阅读说明：本技术 中和1型干扰素的fc融合蛋白及其用途 (FC fusion protein for neutralizing type 1 interferon and application thereof ) 是由 慎英基 李世炯 金成洙 于 2019-12-20 设计创作，主要内容包括：本发明涉及中和1型干扰素的FC融合蛋白及其用途,更具体地说,涉及:包含干扰素受体片段或抗体FC片段的单体在其中结合的二聚体型多肽；其制备方法；以及包含其的药物组合物。本发明的中和1型干扰素的FC融合蛋白阻断1型干扰素和干扰素受体之间的结合,并且具有抑制干扰素的信号传导和生物活性的优异能力,从而能够有效治疗由1型干扰素介导的疾病。(The present invention relates to FC fusion proteins that neutralize type 1 interferon and uses thereof, and more particularly to dimeric polypeptides comprising monomers of an interferon receptor fragment or an antibody FC fragment bound therein; a process for the preparation thereof; and pharmaceutical compositions comprising the same. The FC fusion protein neutralizing type 1 interferon of the present invention blocks the binding between type 1 interferon and interferon receptor, and has excellent ability to inhibit signal transduction and biological activity of interferon, thereby being capable of effectively treating diseases mediated by type 1 interferon.)

具体实施方式

下面将对本发明进行详细的描述。

但是，下面的实施例只是对本发明的说明，本发明的内容并不限于下面的实施例。

实施例1:1型干扰素Fc融合受体蛋白表达载体的制备

利用人类IFNAR1(P17181,28-436aa.)、IFNAR2(P48552,27-243aa.)和IGHG(P01857,100-330aa.)氨基酸序列，构建了一种能够结合或中和1型干扰素蛋白的Fc融合蛋白。如附图1(左)所示，Fc被一个多肽连接子(L；IEGRMD)标记，在所有Fc融合蛋白表达载体中C端，它通过C端和N端之间的IFNAR1或IFNAR2连接，包括Kozac序列(▲)和细胞外分泌诱导信号序列(S)，或直接连接。

如附图1(右)所示，包含每个基因的序列连接在限制性酶NheI和XhoI之间。表达载体分别被命名为pIFNAR1-FcWT、pIFNAR2-FcWT、pIFNAR1-FcA、pIFNAR2-FcB、pIFNAR1-FcB和pLeader-FcA。

对包含多核苷酸序列(SEQ ID NO:1)、IFNAR1的胞外结构域(SEQ ID NO:3)、IFNAR2的胞外结构域(SEQ ID NO:5)、多肽接头(SEQ ID NO:7)和人IGHG的Fc部分(SEQ IDNO:11)以及包含Kozac序列和信号序列的变体(SEQ ID NO:13、SEQ ID NO:15)的基因进行密码子优化，以合成该基因来制备例如图1的核苷酸序列片段。在每个核苷酸序列片段的表达载体(pOptiVec-TOPO)的限制性酶位点中，使用NheI和Xho I之间的T4 DNA连接酶(RBC)制备表达载体。

此外，以相同的方式制备表达载体，除非使用SEQ ID NO:33的接头代替SEQ IDNO:7的多肽接头。换句话说，包含多核苷酸序列(SEQ ID NO:1)、IFNAR1的胞外结构域(SEQID NO:3)、IFNAR2的胞外结构域(SEQ ID NO:5)、多肽接头(SEQ ID NO:33)和人体IGHG的Fc部分(SEQ ID NO:11)以及包含Kozac序列和信号序列的变体(SEQ ID NO:13，SEQ ID NO:13，SEQ ID NO 15)的基因被密码子优化以合成该基因，从而制备图1的核苷酸序列片段e至g。在每个核苷酸序列片段的表达载体的限制性酶位点中，使用NheI和Xho I之间的T4 DNA连接酶(RBC)制备表达载体。

实施例2:蛋白质表达纯化、结构确认和结合确认

以下表述和提纯工艺，旨在使用插入了每种组合的核苷酸序列片段的表达载体生产具有附图2c所示结构的蛋白质。

为了维持每种1型干扰素受体的天然翻译后修饰(PTM)，所有重组蛋白表达都使用根据细胞瞬时表达系统方案的300-600毫升的Expi293TM表达培养基，使用人类衍生的表达细胞Expi293细胞系(Thermo Fisher Scientific)。根据最终的蛋白质，将一个或两个表达载体转染到细胞中，然后根据制造商的方案加入增强子1和2。然后，将培养6天的培养基在6580转/分钟、20分钟和8℃下离心，然后用0.22微米聚乙烯过滤器(康宁)过滤。所有蛋白质都在AKTA前纯化系统(GE通用电气医疗生命科学)中纯化，用20mM磷酸钠、pH 7.2和150mM氯化钠缓冲液以5ml/min的速率填充MabSelect SuRe(GE通用电气医疗生命科学)至柱平均最多为2CV，然后使培养液流动以结合到树脂上。

然后，该重组蛋白在使用5CV的35mM磷酸钠、pH7.2、500mM尔氯化钠缓冲液和1cV的20mM磷酸钠、pH7.2缓冲液柱洗过程后，用100mM柠檬酸盐、pH3.5缓冲液进行洗脱，经过12小时透析并使用4L 1X PBS缓冲液(Biosesang)进行3次透析，使用Amicon UltraCentrifugal过滤器(50K-cut off，Merck Millipore公司生产)将洗脱的蛋白质浓缩至3毫升。使用用于透析的相同缓冲液在Hiload Superdex 200pg(GE医疗保健生命科学)柱上另行将浓缩的重组蛋白与目标蛋白分离。

结果，如附图2a所示，通过大小排阻色谱法比较了每个Fc融合蛋白的大小，预计其具有图2c所示的蛋白质结构。

此外，如图2b所示，分别在天然条件(7.5％Mini-TGXTM Precase蛋白凝胶)、还原条件(Any kDTM Mini-PROTEIN TGXTM Precase蛋白凝胶，Bio-rad)下，确认了IFNAR1/2杂Fc融合蛋白与人体IFNβ-1a之间的结合

本发明氨基酸序列的FC部分包括IGHG1(100-330a.a.)的HINGE部分，以及由氨基酸109-109和112-112形成二硫键形成二聚体。更具体地说，由于FC的CH3部分的特定氨基酸序列的变化，异二聚体的形成主要是从同二聚体到异二聚体。

实施例3:使用Fc融合蛋白的SPR分析

通过附图1和hIFNβ-1a的表达载体组合表达/纯化，分析了I型干扰素中Fc融合蛋白(IFNAR2-Fc异二聚体、IFNAR1/2-Fc异二聚体、IFNAR1-Fc异二聚体)的结合亲和性和动力。

本实验采用(IFNAR1-Fc EW+-Fc RVT)、(IFNAR2-Fc EW+-Fc RVT)和(IFNAR1-FcEW+IFNAR2Fc RVT)分析结合强度和动力。在表达(IFNAR1-Fc RVT+IFNAR2-Fc EW)时，由于确认了同二聚体形式出现多于(IFNAR1-Fc EW+IFNAR2-Fc RVT)的问题，所以没有使用(IFNAR1-Fc RVT+IFNAR2-Fc EW)。

基于Biacore T200(GE医疗生命科学)，使用25℃、30μl/min条件和0.005％DPBST(DPBS/改良、Hyclone和Tween20，Signal)运行缓冲液，所述金质传感器芯片与Anti-HumanFcγ经胺偶联捕获抗体(AffiniPure Goat Anti-Human IgG，Fcγ特异性片段，JacksonImmunoResearch)。在180秒、聚相和600秒、离相条件下测试每种分析物。

如图3所示，根据hIFNb-1a-IFNAR2(1:1拟合模型)、hIFNb-1a-IFNAR1/2(异质配体模型)、hIFNb-1a-IFNAR1(双态结合模型)传感图形状和对接模型预测进行曲线拟合。特别是，IFNAR1/2异源Fc融合蛋白显示出低的KD值。(见表2和表3)

表2

^a传感图用一对一结合模型拟合

^b静态平衡分析使用179.04秒的各个参数进行估计

^c传感图用异源配体模型拟合

表3

^a传感图用双态结合模型拟合

实施例4:通过Fc融合蛋白的配体确认生物活性中和能力

通过以下实验以证实Fc融合蛋白由配体引起的生物活性的中和能力。与实施例3一样，在该实验中使用了(IFNAR1-Fc EW+-Fc RVT)、(IFNAR2-Fc EW+-Fc RVT)和(IFNAR1-Fc EW+IFNAR2Fc RVT)。

所有实验都是基于hIFN-β在Daudi细胞中使用Ez-cytox细胞活力测定试剂盒(Deaillab)的抗增殖作用而设计的，其中每个受体的表达都很高。该试验方法显示了充分地反映配体生物物理特性的试验结果，类似于SPR动力学分析的结果。

具体而言，在96孔板(SPL)中，3×10³细胞的细胞中hIFN-β-1a的含量来确定通过浓度(10nM的IFNAR1-Fc异二聚体、IFNAR2-Fc异二聚体、IFNAR1/2-Fc异二聚体；IFNAR1-Fc异二聚体的6pm；IFNAR1/2-Fc异二聚体)，然后在37℃和5％CO₂的细胞培养箱中进行反应72小时。然后，在根据制造商的方案添加Ex-cytox试剂后，再额外反应3小时后，在450nm处用微孔板读数器(Genios Pro，Tecan)测量，并使用非线性回归分析(GraphPad Prism7.0版软件，美国加利福尼亚州圣地亚哥)比较和分析IC₅₀值。通过单向方差分析(One-way ANOVA)、Bonferroni的多重比较事后检验，证实了本发明每种蛋白质的中和能力具有统计学意义。

如附图4a所示，证实了当干扰素用阻断IFNAR1和IFNAR2结合的Fc融合蛋白处理时，与分别阻断IFNAR1和IFNAR2的融合蛋白的情况相比，干扰素的抗细胞增殖显著降低。

如附图4b所示，当加入根据本发明阻断IFNAR1和IFNAR2的Fc融合蛋白时，IC50值最高。因此，证实了当分别阻断IFNAR1或IFNAR2时，干扰素的抗细胞增殖优于细胞成活力。

如附图4c所示，证实了当具有最高中和能力的IFNAR1/2-Fc异二聚体被应用时，细胞活力以浓度依赖的方式增加。

实施例5:通过IFNAR1/2-Fc异二聚体的配体确认信号机制活性中和能力

以与实施例4相同的方式，除了下面提到的IFNAR1/2-Fc异二聚体之外，确认了通过IFNAR1/2-Fc异二聚体的配体中和生物活性的能力。

具体来说，该组添加了浓度为1nM的IFN(IFN-α1(pbl assay science_cat#11125-1)、IFN-α2a(pbl assay science_cat#11100-1)、IFN-α2b(pbl assay science_cat#11105-1)、IFN-α5(pbl assay science_cat#11135-1)、IFN-α8(pbl assay science_cat#11115-1)、IFN-α10(pbl assay science_cat#11120-1)、IFN-β1a(pbl assay science_cat#11415-1),IFN-ω(pbl assay science_cat#11395)-One)，并且该组中每种干扰素均用浓度为10nm的1型干扰素Fc融合受体蛋白在3×10³细胞群中进行处理，这些细胞在37℃和5％CO₂的细胞培养箱中反应了72小时。然后，在根据制造商的方案添加Ex-cytox试剂后，再额外反应2小时后，在450nm处用微孔板读数器(Genios Pro，Tecan)进行测量，并使用非线性回归分析(GraphPad Prism 7.0版软件，美国加利福尼亚州圣地亚哥)比较和分析IC₅₀值。

结果如附图5所示，证实了当用阻断IFNAR1和IFNAR2结合的IFNAR1/2-Fc异二聚体(使用4GS*3作为连接子)处理IFN-α1、IFN-α2a、IFN-α2b、IFN-α5、IFN-α8、IFN-α10、IFN-β1a、IFN-ω时，与仅用干扰素处理相比，细胞活力显著优越。

通过这些结果，发现通过结合了包含本发明的干扰素受体片段或抗体Fc片段的单体(单体)的二聚体型多肽来调节细胞的过量干扰素信号是可能的，并且通过这一点，证实了它将对1型干扰素介导的疾病如系统性红斑狼疮、干燥综合征、系统性硬化症、肌炎和类风湿关节炎的患者表现出优异的药理学效果，在这些疾病中，响应过量干扰素信号而表达的干扰素诱导基因是高的。

实施例6:通过IFNAR1/2-Fc异二聚体的配体证实化学信号抑制能力

所有实验都是为了证实STAT1及其磷酸化pSTAT1蛋白的变化而进行的，这些变化是通过在Daudi细胞中使用蛋白质印迹的I型干扰素来实现的，其中每个受体的表达都很高。

具体来说，在6孔平板(SPL_第30006类)中，该组添加了浓度为1nM的IFN(IFN-α1(pbl assay science_cat#11125-1)、IFN-α2a(pbl assay science_cat#11100-1)、IFN-α2b(pbl assay science_cat#11105-1)、IFN-α5(pbl assay science_cat#11135-1)、IFN-α8(pbl assay science_cat#11115-1)、IFN-α10(pbl assay science_cat#11120-1)、IFN-β1a(pbl assay science_cat#11415-1)、IFN-ω(pbl assay science_cat#11395-1)、IFN-ε(R&D systems_#9667-ME)，并且该组中每种干扰素均用浓度为10nm的IFNAR1/2-Fc异二聚体蛋白质在2×10⁶细胞群中进行处理，这些细胞在37℃和5％CO₂的细胞培养箱中反应了72小时。然后，从平板上收集细胞，提取总蛋白并用BCA蛋白检测试剂盒(Thermoscientific_#23227)测定。总蛋白通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)在10％凝胶上分离，并转录到聚偏氟乙烯膜上(BIO RAD_#1620177)。在室温下用5％脱脂牛奶、3％牛血清白蛋白、10毫摩尔/升Tris-HCL(pH 8.0)、150毫摩尔/升NaCl和0.05％吐温-20封闭薄膜1小时。所述封闭的薄膜用STAT1抗体(cell signallig_#06-501)、pSTAT1抗体(cell signallig_#58D6)和β肌动蛋白抗体(santa cruz_#sc 47778)作为初级抗体(1:3000稀释)在4℃下处理并过夜。然后，在室温下处理二代酶标抗体、山羊对兔抗体(Invitrogen_#31460)和山羊对鼠抗体(Invitrogen_#g 21040)1小时。用ECL溶液(BIORAD_#1705061)处理所述薄膜后，使用poohung公司的显影剂和定影液将其显现在胶片(Agfa healthcare_#EA8EC)上。

结果如附图6a和6b所示，证实了当用干扰素(IFN-α1、IFN-α2a、IFN-α2b、IFN-α5、IFN-α8、IFN-α10、IFN-β1a)处理阻断IFNAR1和IFNAR2结合的IFNAR1/2-Fc异二聚体(4GS*3)蛋白时，与仅用干扰素处理时pSTAT1蛋白的高磷酸化相比，pSTAT1蛋白的磷酸化显著降低。这表明IFNAR1/2-Fc异二聚体蛋白与1型干扰素结合并表现出中和能力，表明细胞中与干扰素相关的信号传导受到抑制。

工业实用性

本发明的中和Fc融合蛋白1型干扰素具有优异的工业实用性，当阻断1型干扰素与干扰素受体的结合时，具有优异的信号机制起始和生物活性抑制，因此它可以非常有效地用于开发用于预防或治疗1型干扰素介导的疾病治疗药剂。

序列表

<110> 首尔大学校产学协力团

碌园BIO 融合研究财团

<120> 中和1型干扰素的FC融合蛋白及其用途

<130> OP21-0067/PCT/CN

<150> KR 10-2018-0168801

<151> 2018-12-24

<150> PCT/KR 2019/018233

<151> 2019-12-20

<160> 76

<170> KoPatentIn 3.0

<210> 1

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<220>

<223> Kozak-信号序列

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accggcatgg acaactggat caagctgtcc ggctgccaga acatcacctc taccaagtgc 180

aacttctcca gcctgaagct gaacgtgtac gaggaaatca agctgcggat ccgggccgag 240

aaagagaaca ccagcagttg gtacgaggtg gacagcttca cccctttcag aaaggcccag 300

atcggccctc ctgaagtgca cctggaagcc gaggataagg ccatcgtgat ccacatcagc 360

cccggcacca aggactctgt gatgtgggct ctcgacggcc tgtccttcac ctacagcctg 420

gtcatctgga agaactcctc cggcgtggaa gagagaatcg agaacatcta ctcccggcac 480

aagatctaca agctgagccc cgagacaacc tactgcctga aagtgaaggc cgctctgctg 540

acctcctgga agatcggcgt gtactctccc gtgcactgca tcaagaccac cgtggaaaac 600

gagctgcctc ctccagagaa catcgaggtg tccgtgcaga accagaacta cgtgctgaag 660

tgggactaca cctacgccaa catgaccttt caggtgcagt ggctgcacgc ttttctgaag 720

cggaaccctg gcaaccacct gtacaagtgg aagcagattc ccgactgcga gaacgtgaaa 780

accacacagt gcgtgttccc tcagaacgtg ttccagaagg gcatctacct gctgagagtg 840

caggcctccg acggcaacaa caccagcttt tggagcgaag agatcaagtt cgataccgag 900

atccaggcct tcctgctgcc tccagtgttc aacatcagat ccctgtccga ctccttccac 960

atctacatcg gcgctcctaa gcagtccggc aacacccctg tgatccagga ctaccctctg 1020

atctacgaga tcatcttctg ggagaacacc tccaacgccg agcggaagat catcgagaag 1080

aaaaccgacg tgaccgtgcc taacctgaag cctctgaccg tgtactgcgt gaaggctagg 1140

gcccacacca tggacgaaaa gctgaacaag tcctccgtgt tctccgacgc cgtgtgcgaa 1200

aagaccaagc caggcaacac ctctaaa 1227

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Arg Lys Ala Gln Ile Gly Pro Pro Glu Val His Leu Glu Ala Glu Asp

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Lys Ala Ile Val Ile His Ile Ser Pro Gly Thr Lys Asp Ser Val Met

115 120 125

Trp Ala Leu Asp Gly Leu Ser Phe Thr Tyr Ser Leu Val Ile Trp Lys

130 135 140

Asn Ser Ser Gly Val Glu Glu Arg Ile Glu Asn Ile Tyr Ser Arg His

145 150 155 160

Lys Ile Tyr Lys Leu Ser Pro Glu Thr Thr Tyr Cys Leu Lys Val Lys

165 170 175

Ala Ala Leu Leu Thr Ser Trp Lys Ile Gly Val Tyr Ser Pro Val His

180 185 190

Cys Ile Lys Thr Thr Val Glu Asn Glu Leu Pro Pro Pro Glu Asn Ile

195 200 205

Glu Val Ser Val Gln Asn Gln Asn Tyr Val Leu Lys Trp Asp Tyr Thr

210 215 220

Tyr Ala Asn Met Thr Phe Gln Val Gln Trp Leu His Ala Phe Leu Lys

225 230 235 240

Arg Asn Pro Gly Asn His Leu Tyr Lys Trp Lys Gln Ile Pro Asp Cys

245 250 255

Glu Asn Val Lys Thr Thr Gln Cys Val Phe Pro Gln Asn Val Phe Gln

260 265 270

Lys Gly Ile Tyr Leu Leu Arg Val Gln Ala Ser Asp Gly Asn Asn Thr

275 280 285

Ser Phe Trp Ser Glu Glu Ile Lys Phe Asp Thr Glu Ile Gln Ala Phe

290 295 300

Leu Leu Pro Pro Val Phe Asn Ile Arg Ser Leu Ser Asp Ser Phe His

305 310 315 320

Ile Tyr Ile Gly Ala Pro Lys Gln Ser Gly Asn Thr Pro Val Ile Gln

325 330 335

Asp Tyr Pro Leu Ile Tyr Glu Ile Ile Phe Trp Glu Asn Thr Ser Asn

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Ala Glu Arg Lys Ile Ile Glu Lys Lys Thr Asp Val Thr Val Pro Asn

355 360 365

Leu Lys Pro Leu Thr Val Tyr Cys Val Lys Ala Arg Ala His Thr Met

370 375 380

Asp Glu Lys Leu Asn Lys Ser Ser Val Phe Ser Asp Ala Val Cys Glu

385 390 395 400

Lys Thr Lys Pro Gly Asn Thr Ser Lys

405

<210> 5

<211> 651

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2 胞外结构域

<400> 5

atctcctacg acagccctga ctacaccgac gagtcctgca ccttcaagat ctccctgcgg 60

aacttccggt ccatcctgtc ctgggagctg aagaaccact ccatcgtgcc cacacactac 120

accctgctgt acaccatcat gtccaagcct gaggacctga aggtggtcaa gaactgcgcc 180

aacaccacca gatctttctg cgacctgacc gatgagtggc ggtctaccca cgaggcttac 240

gtgacagtgc tggaaggctt ctccggcaat accacactgt tcagctgctc ccacaacttc 300

tggctggcca tcgacatgtc cttcgagcct ccagagttcg agatcgtggg cttcaccaac 360

cacatcaacg tgatggtcaa gttccccagc atcgtggaag aggaactcca gttcgacctg 420

agcctggtca tcgaggaaca gtccgagggc atcgtgaaga agcacaagcc cgagatcaag 480

ggcaacatgt ccggcaactt cacctacatc atcgacaagc tgatccccaa caccaactac 540

tgcgtgtccg tgtacctgga acactccgat gagcaggccg tgatcaagtc ccctctgaag 600

tgtaccctgc tgcctcctgg ccaagagtct gagtctgccg agtctgctaa a 651

<210> 6

<211> 217

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2 胞外结构域

<400> 6

Ile Ser Tyr Asp Ser Pro Asp Tyr Thr Asp Glu Ser Cys Thr Phe Lys

1 5 10 15

Ile Ser Leu Arg Asn Phe Arg Ser Ile Leu Ser Trp Glu Leu Lys Asn

20 25 30

His Ser Ile Val Pro Thr His Tyr Thr Leu Leu Tyr Thr Ile Met Ser

35 40 45

Lys Pro Glu Asp Leu Lys Val Val Lys Asn Cys Ala Asn Thr Thr Arg

50 55 60

Ser Phe Cys Asp Leu Thr Asp Glu Trp Arg Ser Thr His Glu Ala Tyr

65 70 75 80

Val Thr Val Leu Glu Gly Phe Ser Gly Asn Thr Thr Leu Phe Ser Cys

85 90 95

Ser His Asn Phe Trp Leu Ala Ile Asp Met Ser Phe Glu Pro Pro Glu

100 105 110

Phe Glu Ile Val Gly Phe Thr Asn His Ile Asn Val Met Val Lys Phe

115 120 125

Pro Ser Ile Val Glu Glu Glu Leu Gln Phe Asp Leu Ser Leu Val Ile

130 135 140

Glu Glu Gln Ser Glu Gly Ile Val Lys Lys His Lys Pro Glu Ile Lys

145 150 155 160

Gly Asn Met Ser Gly Asn Phe Thr Tyr Ile Ile Asp Lys Leu Ile Pro

165 170 175

Asn Thr Asn Tyr Cys Val Ser Val Tyr Leu Glu His Ser Asp Glu Gln

180 185 190

Ala Val Ile Lys Ser Pro Leu Lys Cys Thr Leu Leu Pro Pro Gly Gln

195 200 205

Glu Ser Glu Ser Ala Glu Ser Ala Lys

210 215

<210> 7

<211> 696

<212> DNA

<213> 人工序列

<220>

<223> FC-WT

<400> 7

cccaagagct gcgacaagac ccacacctgt cccccctgcc ctgcccctga actgctgggc 60

ggacccagcg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 120

cccgaagtga cctgcgtggt ggtggacgtg tcccacgagg accctgaagt gaagttcaat 180

tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagtac 240

aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 300

aaagagtaca agtgcaaggt gtccaacaag gccctgcctg cccccatcga gaaaaccatc 360

agcaaggcca agggccagcc ccgcgagccc caggtgtaca cactgccccc cagccgggac 420

gagctgacca agaaccaggt gtccctgacc tgcctggtga aaggcttcta ccccagcgat 480

atcgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 540

gtgctggaca gcgacggctc attcttcctg tacagcaagc tgaccgtgga caagagccgg 600

tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 660

acccagaagt ccctgagcct gagccccggc aagtag 696

<210> 8

<211> 231

<212> PRT

<213> 人工序列

<220>

<223> FC-WT

<400> 8

Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro

1 5 10 15

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

20 25 30

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

35 40 45

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

50 55 60

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

65 70 75 80

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

85 90 95

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105 110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120 125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys

130 135 140

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

145 150 155 160

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

165 170 175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

180 185 190

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

195 200 205

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

210 215 220

Leu Ser Leu Ser Pro Gly Lys

225 230

<210> 9

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> 连接子

<400> 9

atcgagggcc ggatggac 18

<210> 10

<211> 6

<212> PRT

<213> 人工序列

<220>

<223> 连接子

<400> 10

Ile Glu Gly Arg Met Asp

1 5

<210> 11

<211> 696

<212> DNA

<213> 人工序列

<220>

<223> FC-EW

<400> 11

cccaagagct gcgacaagac ccacacctgt cccccctgcc ctgcccctga actgctgggc 60

ggacccagcg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 120

cccgaagtga cctgcgtggt ggtggacgtg tcccacgagg accctgaagt gaagttcaat 180

tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagtac 240

aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 300

aaagagtaca agtgcaaggt gtccaacaag gccctgcctg cccccatcga gaaaaccatc 360

agcaaggcca agggccagcc ccgcgagccc caggtgtaca cactgccccc cagccgggac 420

gagctgaccg agaaccaggt gtccctgacc tgcctggtga aaggcttcta ccccagcgat 480

atcgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 540

gtgctggaca gcgacggctc attcttcctg tacagctggc tgaccgtgga caagagccgg 600

tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 660

acccagaagt ccctgagcct gagccccggc aagtag 696

<210> 12

<211> 231

<212> PRT

<213> 人工序列

<220>

<223> FC-EW

<400> 12

Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro

1 5 10 15

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

20 25 30

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

35 40 45

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

50 55 60

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

65 70 75 80

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

85 90 95

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105 110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120 125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Glu

130 135 140

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

145 150 155 160

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

165 170 175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

180 185 190

Trp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

195 200 205

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

210 215 220

Leu Ser Leu Ser Pro Gly Lys

225 230

<210> 13

<211> 696

<212> DNA

<213> 人工序列

<220>

<223> FC-RVT

<400> 13

cccaagagct gcgacaagac ccacacctgt cccccctgcc ctgcccctga actgctgggc 60

ggacccagcg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 120

cccgaagtga cctgcgtggt ggtggacgtg tcccacgagg accctgaagt gaagttcaat 180

tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagtac 240

aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 300

aaagagtaca agtgcaaggt gtccaacaag gccctgcctg cccccatcga gaaaaccatc 360

agcaaggcca agggccagcc ccgcgagccc cgggtgtaca cactgccccc cagccgggac 420

gagctgacca agaaccaggt gtccctgacc tgcctggtga aaggcttcta ccccagcgat 480

atcgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 540

gtgctggtca gcgacggctc attcaccctg tacagcaagc tgaccgtgga caagagccgg 600

tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 660

acccagaagt ccctgagcct gagccccggc aagtag 696

<210> 14

<211> 231

<212> PRT

<213> 人工序列

<220>

<223> FC-RVT

<400> 14

Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro

1 5 10 15

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

20 25 30

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

35 40 45

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

50 55 60

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

65 70 75 80

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

85 90 95

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105 110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120 125

Glu Pro Arg Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys

130 135 140

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

145 150 155 160

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

165 170 175

Thr Thr Pro Pro Val Leu Val Ser Asp Gly Ser Phe Thr Leu Tyr Ser

180 185 190

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

195 200 205

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

210 215 220

Leu Ser Leu Ser Pro Gly Lys

225 230

<210> 15

<211> 783

<212> DNA

<213> 人工序列

<220>

<223> 连接子-FC WT

<400> 15

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tcgagggccg gatggacccc aagagctgcg acaagaccca cacctgtccc 120

ccctgccctg cccctgaact gctgggcgga cccagcgtgt tcctgttccc cccaaagccc 180

aaggacaccc tgatgatcag ccggaccccc gaagtgacct gcgtggtggt ggacgtgtcc 240

cacgaggacc ctgaagtgaa gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 300

aagaccaagc ccagagagga acagtacaac agcacctacc gggtggtgtc cgtgctgacc 360

gtgctgcacc aggactggct gaacggcaaa gagtacaagt gcaaggtgtc caacaaggcc 420

ctgcctgccc ccatcgagaa aaccatcagc aaggccaagg gccagccccg cgagccccag 480

gtgtacacac tgccccccag ccgggacgag ctgaccaaga accaggtgtc cctgacctgc 540

ctggtgaaag gcttctaccc cagcgatatc gccgtggaat gggagagcaa cggccagccc 600

gagaacaact acaagaccac cccccctgtg ctggacagcg acggctcatt cttcctgtac 660

agcaagctga ccgtggacaa gagccggtgg cagcagggca acgtgttcag ctgcagcgtg 720

atgcacgagg ccctgcacaa ccactacacc cagaagtccc tgagcctgag ccccggcaag 780

tga 783

<210> 16

<211> 260

<212> PRT

<213> 人工序列

<220>

<223> 连接子-FC WT

<400> 16

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Glu Gly Arg Met Asp Pro Lys Ser

20 25 30

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

35 40 45

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

50 55 60

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

65 70 75 80

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

85 90 95

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

100 105 110

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

115 120 125

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

130 135 140

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

145 150 155 160

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

165 170 175

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

180 185 190

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

195 200 205

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

210 215 220

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

225 230 235 240

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

245 250 255

Ser Pro Gly Lys

260

<210> 17

<211> 783

<212> DNA

<213> 人工序列

<220>

<223> 连接子-FC EW

<400> 17

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tcgagggccg gatggacccc aagagctgcg acaagaccca cacctgtccc 120

ccctgccctg cccctgaact gctgggcgga cccagcgtgt tcctgttccc cccaaagccc 180

aaggacaccc tgatgatcag ccggaccccc gaagtgacct gcgtggtggt ggacgtgtcc 240

cacgaggacc ctgaagtgaa gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 300

aagaccaagc ccagagagga acagtacaac agcacctacc gggtggtgtc cgtgctgacc 360

gtgctgcacc aggactggct gaacggcaaa gagtacaagt gcaaggtgtc caacaaggcc 420

ctgcctgccc ccatcgagaa aaccatcagc aaggccaagg gccagccccg cgagccccag 480

gtgtacacac tgccccccag ccgggacgag ctgaccgaga accaggtgtc cctgacctgc 540

ctggtgaaag gcttctaccc cagcgatatc gccgtggaat gggagagcaa cggccagccc 600

gagaacaact acaagaccac cccccctgtg ctggacagcg acggctcatt cttcctgtac 660

agctggctga ccgtggacaa gagccggtgg cagcagggca acgtgttcag ctgcagcgtg 720

atgcacgagg ccctgcacaa ccactacacc cagaagtccc tgagcctgag ccccggcaag 780

tag 783

<210> 18

<211> 260

<212> PRT

<213> 人工序列

<220>

<223> 连接子-FC EW

<400> 18

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Glu Gly Arg Met Asp Pro Lys Ser

20 25 30

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

35 40 45

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

50 55 60

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

65 70 75 80

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

85 90 95

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

100 105 110

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

115 120 125

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

130 135 140

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

145 150 155 160

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Glu Asn Gln Val

165 170 175

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

180 185 190

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

195 200 205

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Trp Leu Thr

210 215 220

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

225 230 235 240

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

245 250 255

Ser Pro Gly Lys

260

<210> 19

<211> 783

<212> DNA

<213> 人工序列

<220>

<223> 连接子-FC RVT

<400> 19

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tcgagggccg gatggacccc aagagctgcg acaagaccca cacctgtccc 120

ccctgccctg cccctgaact gctgggcgga cccagcgtgt tcctgttccc cccaaagccc 180

aaggacaccc tgatgatcag ccggaccccc gaagtgacct gcgtggtggt ggacgtgtcc 240

cacgaggacc ctgaagtgaa gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 300

aagaccaagc ccagagagga acagtacaac agcacctacc gggtggtgtc cgtgctgacc 360

gtgctgcacc aggactggct gaacggcaaa gagtacaagt gcaaggtgtc caacaaggcc 420

ctgcctgccc ccatcgagaa aaccatcagc aaggccaagg gccagccccg cgagccccgg 480

gtgtacacac tgccccccag ccgggacgag ctgaccaaga accaggtgtc cctgacctgc 540

ctggtgaaag gcttctaccc cagcgatatc gccgtggaat gggagagcaa cggccagccc 600

gagaacaact acaagaccac cccccctgtg ctggtcagcg acggctcatt caccctgtac 660

agcaagctga ccgtggacaa gagccggtgg cagcagggca acgtgttcag ctgcagcgtg 720

atgcacgagg ccctgcacaa ccactacacc cagaagtccc tgagcctgag ccccggcaag 780

tag 783

<210> 20

<211> 260

<212> PRT

<213> 人工序列

<220>

<223> 连接子-FC RVT

<400> 20

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Glu Gly Arg Met Asp Pro Lys Ser

20 25 30

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

35 40 45

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

50 55 60

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

65 70 75 80

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

85 90 95

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

100 105 110

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

115 120 125

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

130 135 140

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Arg

145 150 155 160

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

165 170 175

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

180 185 190

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

195 200 205

Pro Val Leu Val Ser Asp Gly Ser Phe Thr Leu Tyr Ser Lys Leu Thr

210 215 220

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

225 230 235 240

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

245 250 255

Ser Pro Gly Lys

260

<210> 21

<211> 2010

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC WT

<400> 21

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaatcg agggccggat ggaccccaag 1320

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 1380

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 1440

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 1500

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 1560

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 1620

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 1680

gccaagggcc agccccgcga gccccaggtg tacacactgc cccccagccg ggacgagctg 1740

accaagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 1800

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1860

gacagcgacg gctcattctt cctgtacagc aagctgaccg tggacaagag ccggtggcag 1920

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 1980

aagtccctga gcctgagccc cggcaagtga 2010

<210> 22

<211> 669

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC WT

<400> 22

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

435 440 445

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

450 455 460

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

465 470 475 480

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

485 490 495

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

500 505 510

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

515 520 525

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

530 535 540

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

545 550 555 560

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

565 570 575

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

580 585 590

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

595 600 605

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

610 615 620

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

625 630 635 640

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

645 650 655

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

660 665

<210> 23

<211> 2010

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC EW

<400> 23

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaatcg agggccggat ggaccccaag 1320

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 1380

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 1440

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 1500

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 1560

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 1620

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 1680

gccaagggcc agccccgcga gccccaggtg tacacactgc cccccagccg ggacgagctg 1740

accgagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 1800

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1860

gacagcgacg gctcattctt cctgtacagc tggctgaccg tggacaagag ccggtggcag 1920

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 1980

aagtccctga gcctgagccc cggcaagtag 2010

<210> 24

<211> 669

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC EW

<400> 24

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

435 440 445

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

450 455 460

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

465 470 475 480

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

485 490 495

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

500 505 510

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

515 520 525

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

530 535 540

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

545 550 555 560

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

565 570 575

Arg Asp Glu Leu Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Lys

580 585 590

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

595 600 605

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

610 615 620

Ser Phe Phe Leu Tyr Ser Trp Leu Thr Val Asp Lys Ser Arg Trp Gln

625 630 635 640

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

645 650 655

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

660 665

<210> 25

<211> 2010

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC RVT

<400> 25

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaatcg agggccggat ggaccccaag 1320

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 1380

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 1440

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 1500

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 1560

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 1620

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 1680

gccaagggcc agccccgcga gccccgggtg tacacactgc cccccagccg ggacgagctg 1740

accaagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 1800

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1860

gtcagcgacg gctcattcac cctgtacagc aagctgaccg tggacaagag ccggtggcag 1920

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 1980

aagtccctga gcctgagccc cggcaagtag 2010

<210> 26

<211> 669

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子-FC RVT

<400> 26

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

435 440 445

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

450 455 460

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

465 470 475 480

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

485 490 495

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

500 505 510

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

515 520 525

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

530 535 540

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

545 550 555 560

Ala Lys Gly Gln Pro Arg Glu Pro Arg Val Tyr Thr Leu Pro Pro Ser

565 570 575

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

580 585 590

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

595 600 605

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Val Ser Asp Gly

610 615 620

Ser Phe Thr Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

625 630 635 640

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

645 650 655

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

660 665

<210> 27

<211> 1434

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC WT

<400> 27

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

atcgagggcc ggatggaccc caagagctgc gacaagaccc acacctgtcc cccctgccct 780

gcccctgaac tgctgggcgg acccagcgtg ttcctgttcc ccccaaagcc caaggacacc 840

ctgatgatca gccggacccc cgaagtgacc tgcgtggtgg tggacgtgtc ccacgaggac 900

cctgaagtga agttcaattg gtacgtggac ggcgtggaag tgcacaacgc caagaccaag 960

cccagagagg aacagtacaa cagcacctac cgggtggtgt ccgtgctgac cgtgctgcac 1020

caggactggc tgaacggcaa agagtacaag tgcaaggtgt ccaacaaggc cctgcctgcc 1080

cccatcgaga aaaccatcag caaggccaag ggccagcccc gcgagcccca ggtgtacaca 1140

ctgcccccca gccgggacga gctgaccaag aaccaggtgt ccctgacctg cctggtgaaa 1200

ggcttctacc ccagcgatat cgccgtggaa tgggagagca acggccagcc cgagaacaac 1260

tacaagacca ccccccctgt gctggacagc gacggctcat tcttcctgta cagcaagctg 1320

accgtggaca agagccggtg gcagcagggc aacgtgttca gctgcagcgt gatgcacgag 1380

gccctgcaca accactacac ccagaagtcc ctgagcctga gccccggcaa gtga 1434

<210> 28

<211> 477

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC WT

<400> 28

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

245 250 255

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

260 265 270

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

275 280 285

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

290 295 300

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

305 310 315 320

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

325 330 335

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

340 345 350

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

355 360 365

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

370 375 380

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

385 390 395 400

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

405 410 415

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

420 425 430

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

435 440 445

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

450 455 460

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

465 470 475

<210> 29

<211> 1434

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC EW

<400> 29

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

atcgagggcc ggatggaccc caagagctgc gacaagaccc acacctgtcc cccctgccct 780

gcccctgaac tgctgggcgg acccagcgtg ttcctgttcc ccccaaagcc caaggacacc 840

ctgatgatca gccggacccc cgaagtgacc tgcgtggtgg tggacgtgtc ccacgaggac 900

cctgaagtga agttcaattg gtacgtggac ggcgtggaag tgcacaacgc caagaccaag 960

cccagagagg aacagtacaa cagcacctac cgggtggtgt ccgtgctgac cgtgctgcac 1020

caggactggc tgaacggcaa agagtacaag tgcaaggtgt ccaacaaggc cctgcctgcc 1080

cccatcgaga aaaccatcag caaggccaag ggccagcccc gcgagcccca ggtgtacaca 1140

ctgcccccca gccgggacga gctgaccgag aaccaggtgt ccctgacctg cctggtgaaa 1200

ggcttctacc ccagcgatat cgccgtggaa tgggagagca acggccagcc cgagaacaac 1260

tacaagacca ccccccctgt gctggacagc gacggctcat tcttcctgta cagctggctg 1320

accgtggaca agagccggtg gcagcagggc aacgtgttca gctgcagcgt gatgcacgag 1380

gccctgcaca accactacac ccagaagtcc ctgagcctga gccccggcaa gtag 1434

<210> 30

<211> 477

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC EW

<400> 30

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

245 250 255

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

260 265 270

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

275 280 285

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

290 295 300

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

305 310 315 320

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

325 330 335

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

340 345 350

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

355 360 365

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

370 375 380

Arg Asp Glu Leu Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Lys

385 390 395 400

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

405 410 415

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

420 425 430

Ser Phe Phe Leu Tyr Ser Trp Leu Thr Val Asp Lys Ser Arg Trp Gln

435 440 445

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

450 455 460

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

465 470 475

<210> 31

<211> 1434

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC RVT

<400> 31

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

atcgagggcc ggatggaccc caagagctgc gacaagaccc acacctgtcc cccctgccct 780

gcccctgaac tgctgggcgg acccagcgtg ttcctgttcc ccccaaagcc caaggacacc 840

ctgatgatca gccggacccc cgaagtgacc tgcgtggtgg tggacgtgtc ccacgaggac 900

cctgaagtga agttcaattg gtacgtggac ggcgtggaag tgcacaacgc caagaccaag 960

cccagagagg aacagtacaa cagcacctac cgggtggtgt ccgtgctgac cgtgctgcac 1020

caggactggc tgaacggcaa agagtacaag tgcaaggtgt ccaacaaggc cctgcctgcc 1080

cccatcgaga aaaccatcag caaggccaag ggccagcccc gcgagccccg ggtgtacaca 1140

ctgcccccca gccgggacga gctgaccaag aaccaggtgt ccctgacctg cctggtgaaa 1200

ggcttctacc ccagcgatat cgccgtggaa tgggagagca acggccagcc cgagaacaac 1260

tacaagacca ccccccctgt gctggtcagc gacggctcat tcaccctgta cagcaagctg 1320

accgtggaca agagccggtg gcagcagggc aacgtgttca gctgcagcgt gatgcacgag 1380

gccctgcaca accactacac ccagaagtcc ctgagcctga gccccggcaa gtag 1434

<210> 32

<211> 477

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子-FC RVT

<400> 32

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Ile Glu Gly Arg Met Asp Pro Lys Ser Cys Asp Lys Thr His Thr Cys

245 250 255

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

260 265 270

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

275 280 285

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

290 295 300

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

305 310 315 320

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

325 330 335

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

340 345 350

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

355 360 365

Ala Lys Gly Gln Pro Arg Glu Pro Arg Val Tyr Thr Leu Pro Pro Ser

370 375 380

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

385 390 395 400

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

405 410 415

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Val Ser Asp Gly

420 425 430

Ser Phe Thr Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

435 440 445

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

450 455 460

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

465 470 475

<210> 33

<211> 45

<212> DNA

<213> 人工序列

<220>

<223> 连接子_4GS*3

<400> 33

ggcggcggag gatctggcgg aggtggaagc ggaggcggtg gatct 45

<210> 34

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*3

<400> 34

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10 15

<210> 35

<211> 810

<212> DNA

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC WT

<400> 35

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggccg gcggcggagg atctggcgga ggtggaagcg gaggcggtgg atctcccaag 120

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 180

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 240

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 300

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 360

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 420

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 480

gccaagggcc agccccgcga gccccaggtg tacacactgc cccccagccg ggacgagctg 540

accaagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 600

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 660

gacagcgacg gctcattctt cctgtacagc aagctgaccg tggacaagag ccggtggcag 720

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 780

aagtccctga gcctgagccc cggcaagtga 810

<210> 36

<211> 269

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC WT

<400> 36

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Pro Lys Ser Cys Asp Lys Thr His Thr Cys

35 40 45

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

50 55 60

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

65 70 75 80

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

85 90 95

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

100 105 110

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

115 120 125

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

130 135 140

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

145 150 155 160

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

165 170 175

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

180 185 190

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

195 200 205

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

210 215 220

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

225 230 235 240

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

245 250 255

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

260 265

<210> 37

<211> 810

<212> DNA

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC EW

<400> 37

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggccg gcggcggagg atctggcgga ggtggaagcg gaggcggtgg atctcccaag 120

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 180

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 240

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 300

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 360

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 420

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 480

gccaagggcc agccccgcga gccccaggtg tacacactgc cccccagccg ggacgagctg 540

accgagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 600

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 660

gacagcgacg gctcattctt cctgtacagc tggctgaccg tggacaagag ccggtggcag 720

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 780

aagtccctga gcctgagccc cggcaagtag 810

<210> 38

<211> 269

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC EW

<400> 38

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Pro Lys Ser Cys Asp Lys Thr His Thr Cys

35 40 45

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

50 55 60

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

65 70 75 80

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

85 90 95

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

100 105 110

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

115 120 125

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

130 135 140

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

145 150 155 160

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

165 170 175

Arg Asp Glu Leu Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Lys

180 185 190

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

195 200 205

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

210 215 220

Ser Phe Phe Leu Tyr Ser Trp Leu Thr Val Asp Lys Ser Arg Trp Gln

225 230 235 240

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

245 250 255

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

260 265

<210> 39

<211> 810

<212> DNA

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC RVT

<400> 39

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggccg gcggcggagg atctggcgga ggtggaagcg gaggcggtgg atctcccaag 120

agctgcgaca agacccacac ctgtcccccc tgccctgccc ctgaactgct gggcggaccc 180

agcgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 240

gtgacctgcg tggtggtgga cgtgtcccac gaggaccctg aagtgaagtt caattggtac 300

gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gtacaacagc 360

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 420

tacaagtgca aggtgtccaa caaggccctg cctgccccca tcgagaaaac catcagcaag 480

gccaagggcc agccccgcga gccccgggtg tacacactgc cccccagccg ggacgagctg 540

accaagaacc aggtgtccct gacctgcctg gtgaaaggct tctaccccag cgatatcgcc 600

gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 660

gtcagcgacg gctcattcac cctgtacagc aagctgaccg tggacaagag ccggtggcag 720

cagggcaacg tgttcagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 780

aagtccctga gcctgagccc cggcaagtag 810

<210> 40

<211> 269

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*3-FC RVT

<400> 40

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly

20 25 30

Ser Gly Gly Gly Gly Ser Pro Lys Ser Cys Asp Lys Thr His Thr Cys

35 40 45

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

50 55 60

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

65 70 75 80

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

85 90 95

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

100 105 110

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

115 120 125

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

130 135 140

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

145 150 155 160

Ala Lys Gly Gln Pro Arg Glu Pro Arg Val Tyr Thr Leu Pro Pro Ser

165 170 175

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

180 185 190

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

195 200 205

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Val Ser Asp Gly

210 215 220

Ser Phe Thr Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

225 230 235 240

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

245 250 255

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

260 265

<210> 41

<211> 2037

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC WT

<400> 41

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaggcg gcggaggatc tggcggaggt 1320

ggaagcggag gcggtggatc tcccaagagc tgcgacaaga cccacacctg tcccccctgc 1380

cctgcccctg aactgctggg cggacccagc gtgttcctgt tccccccaaa gcccaaggac 1440

accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggacgt gtcccacgag 1500

gaccctgaag tgaagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1560

aagcccagag aggaacagta caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1620

caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa ggccctgcct 1680

gcccccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc ccaggtgtac 1740

acactgcccc ccagccggga cgagctgacc aagaaccagg tgtccctgac ctgcctggtg 1800

aaaggcttct accccagcga tatcgccgtg gaatgggaga gcaacggcca gcccgagaac 1860

aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct gtacagcaag 1920

ctgaccgtgg acaagagccg gtggcagcag ggcaacgtgt tcagctgcag cgtgatgcac 1980

gaggccctgc acaaccacta cacccagaag tccctgagcc tgagccccgg caagtga 2037

<210> 42

<211> 678

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC WT

<400> 42

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 43

<211> 2037

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC EW

<400> 43

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaggcg gcggaggatc tggcggaggt 1320

ggaagcggag gcggtggatc tcccaagagc tgcgacaaga cccacacctg tcccccctgc 1380

cctgcccctg aactgctggg cggacccagc gtgttcctgt tccccccaaa gcccaaggac 1440

accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggacgt gtcccacgag 1500

gaccctgaag tgaagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1560

aagcccagag aggaacagta caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1620

caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa ggccctgcct 1680

gcccccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc ccaggtgtac 1740

acactgcccc ccagccggga cgagctgacc gagaaccagg tgtccctgac ctgcctggtg 1800

aaaggcttct accccagcga tatcgccgtg gaatgggaga gcaacggcca gcccgagaac 1860

aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct gtacagctgg 1920

ctgaccgtgg acaagagccg gtggcagcag ggcaacgtgt tcagctgcag cgtgatgcac 1980

gaggccctgc acaaccacta cacccagaag tccctgagcc tgagccccgg caagtag 2037

<210> 44

<211> 678

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC EW

<400> 44

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Glu Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Trp

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 45

<211> 2037

<212> DNA

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC RVT

<400> 45

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca agaacctgaa gtcccctcag aaagtggaag tggacatcat cgacgacaac 120

ttcatcctgc ggtggaacag atccgacgag tccgtgggca acgtgacctt cagcttcgac 180

taccagaaaa ccggcatgga caactggatc aagctgtccg gctgccagaa catcacctct 240

accaagtgca acttctccag cctgaagctg aacgtgtacg aggaaatcaa gctgcggatc 300

cgggccgaga aagagaacac cagcagttgg tacgaggtgg acagcttcac ccctttcaga 360

aaggcccaga tcggccctcc tgaagtgcac ctggaagccg aggataaggc catcgtgatc 420

cacatcagcc ccggcaccaa ggactctgtg atgtgggctc tcgacggcct gtccttcacc 480

tacagcctgg tcatctggaa gaactcctcc ggcgtggaag agagaatcga gaacatctac 540

tcccggcaca agatctacaa gctgagcccc gagacaacct actgcctgaa agtgaaggcc 600

gctctgctga cctcctggaa gatcggcgtg tactctcccg tgcactgcat caagaccacc 660

gtggaaaacg agctgcctcc tccagagaac atcgaggtgt ccgtgcagaa ccagaactac 720

gtgctgaagt gggactacac ctacgccaac atgacctttc aggtgcagtg gctgcacgct 780

tttctgaagc ggaaccctgg caaccacctg tacaagtgga agcagattcc cgactgcgag 840

aacgtgaaaa ccacacagtg cgtgttccct cagaacgtgt tccagaaggg catctacctg 900

ctgagagtgc aggcctccga cggcaacaac accagctttt ggagcgaaga gatcaagttc 960

gataccgaga tccaggcctt cctgctgcct ccagtgttca acatcagatc cctgtccgac 1020

tccttccaca tctacatcgg cgctcctaag cagtccggca acacccctgt gatccaggac 1080

taccctctga tctacgagat catcttctgg gagaacacct ccaacgccga gcggaagatc 1140

atcgagaaga aaaccgacgt gaccgtgcct aacctgaagc ctctgaccgt gtactgcgtg 1200

aaggctaggg cccacaccat ggacgaaaag ctgaacaagt cctccgtgtt ctccgacgcc 1260

gtgtgcgaaa agaccaagcc aggcaacacc tctaaaggcg gcggaggatc tggcggaggt 1320

ggaagcggag gcggtggatc tcccaagagc tgcgacaaga cccacacctg tcccccctgc 1380

cctgcccctg aactgctggg cggacccagc gtgttcctgt tccccccaaa gcccaaggac 1440

accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggacgt gtcccacgag 1500

gaccctgaag tgaagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1560

aagcccagag aggaacagta caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1620

caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa ggccctgcct 1680

gcccccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc ccgggtgtac 1740

acactgcccc ccagccggga cgagctgacc aagaaccagg tgtccctgac ctgcctggtg 1800

aaaggcttct accccagcga tatcgccgtg gaatgggaga gcaacggcca gcccgagaac 1860

aactacaaga ccaccccccc tgtgctggtc agcgacggct cattcaccct gtacagcaag 1920

ctgaccgtgg acaagagccg gtggcagcag ggcaacgtgt tcagctgcag cgtgatgcac 1980

gaggccctgc acaaccacta cacccagaag tccctgagcc tgagccccgg caagtag 2037

<210> 46

<211> 678

<212> PRT

<213> 人工序列

<220>

<223> IFNAR1-连接子_4GS*3-FC RVT

<400> 46

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Lys Asn Leu Lys Ser Pro Gln Lys Val

20 25 30

Glu Val Asp Ile Ile Asp Asp Asn Phe Ile Leu Arg Trp Asn Arg Ser

35 40 45

Asp Glu Ser Val Gly Asn Val Thr Phe Ser Phe Asp Tyr Gln Lys Thr

50 55 60

Gly Met Asp Asn Trp Ile Lys Leu Ser Gly Cys Gln Asn Ile Thr Ser

65 70 75 80

Thr Lys Cys Asn Phe Ser Ser Leu Lys Leu Asn Val Tyr Glu Glu Ile

85 90 95

Lys Leu Arg Ile Arg Ala Glu Lys Glu Asn Thr Ser Ser Trp Tyr Glu

100 105 110

Val Asp Ser Phe Thr Pro Phe Arg Lys Ala Gln Ile Gly Pro Pro Glu

115 120 125

Val His Leu Glu Ala Glu Asp Lys Ala Ile Val Ile His Ile Ser Pro

130 135 140

Gly Thr Lys Asp Ser Val Met Trp Ala Leu Asp Gly Leu Ser Phe Thr

145 150 155 160

Tyr Ser Leu Val Ile Trp Lys Asn Ser Ser Gly Val Glu Glu Arg Ile

165 170 175

Glu Asn Ile Tyr Ser Arg His Lys Ile Tyr Lys Leu Ser Pro Glu Thr

180 185 190

Thr Tyr Cys Leu Lys Val Lys Ala Ala Leu Leu Thr Ser Trp Lys Ile

195 200 205

Gly Val Tyr Ser Pro Val His Cys Ile Lys Thr Thr Val Glu Asn Glu

210 215 220

Leu Pro Pro Pro Glu Asn Ile Glu Val Ser Val Gln Asn Gln Asn Tyr

225 230 235 240

Val Leu Lys Trp Asp Tyr Thr Tyr Ala Asn Met Thr Phe Gln Val Gln

245 250 255

Trp Leu His Ala Phe Leu Lys Arg Asn Pro Gly Asn His Leu Tyr Lys

260 265 270

Trp Lys Gln Ile Pro Asp Cys Glu Asn Val Lys Thr Thr Gln Cys Val

275 280 285

Phe Pro Gln Asn Val Phe Gln Lys Gly Ile Tyr Leu Leu Arg Val Gln

290 295 300

Ala Ser Asp Gly Asn Asn Thr Ser Phe Trp Ser Glu Glu Ile Lys Phe

305 310 315 320

Asp Thr Glu Ile Gln Ala Phe Leu Leu Pro Pro Val Phe Asn Ile Arg

325 330 335

Ser Leu Ser Asp Ser Phe His Ile Tyr Ile Gly Ala Pro Lys Gln Ser

340 345 350

Gly Asn Thr Pro Val Ile Gln Asp Tyr Pro Leu Ile Tyr Glu Ile Ile

355 360 365

Phe Trp Glu Asn Thr Ser Asn Ala Glu Arg Lys Ile Ile Glu Lys Lys

370 375 380

Thr Asp Val Thr Val Pro Asn Leu Lys Pro Leu Thr Val Tyr Cys Val

385 390 395 400

Lys Ala Arg Ala His Thr Met Asp Glu Lys Leu Asn Lys Ser Ser Val

405 410 415

Phe Ser Asp Ala Val Cys Glu Lys Thr Lys Pro Gly Asn Thr Ser Lys

420 425 430

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Arg Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Val Ser Asp Gly Ser Phe Thr Leu Tyr Ser Lys

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 47

<211> 1461

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC WT

<400> 47

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

ggcggcggag gatctggcgg aggtggaagc ggaggcggtg gatctcccaa gagctgcgac 780

aagacccaca cctgtccccc ctgccctgcc cctgaactgc tgggcggacc cagcgtgttc 840

ctgttccccc caaagcccaa ggacaccctg atgatcagcc ggacccccga agtgacctgc 900

gtggtggtgg acgtgtccca cgaggaccct gaagtgaagt tcaattggta cgtggacggc 960

gtggaagtgc acaacgccaa gaccaagccc agagaggaac agtacaacag cacctaccgg 1020

gtggtgtccg tgctgaccgt gctgcaccag gactggctga acggcaaaga gtacaagtgc 1080

aaggtgtcca acaaggccct gcctgccccc atcgagaaaa ccatcagcaa ggccaagggc 1140

cagccccgcg agccccaggt gtacacactg ccccccagcc gggacgagct gaccaagaac 1200

caggtgtccc tgacctgcct ggtgaaaggc ttctacccca gcgatatcgc cgtggaatgg 1260

gagagcaacg gccagcccga gaacaactac aagaccaccc cccctgtgct ggacagcgac 1320

ggctcattct tcctgtacag caagctgacc gtggacaaga gccggtggca gcagggcaac 1380

gtgttcagct gcagcgtgat gcacgaggcc ctgcacaacc actacaccca gaagtccctg 1440

agcctgagcc ccggcaagtg a 1461

<210> 48

<211> 486

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC WT

<400> 48

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

245 250 255

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

260 265 270

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

275 280 285

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

290 295 300

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

305 310 315 320

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

325 330 335

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

340 345 350

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

355 360 365

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

370 375 380

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

385 390 395 400

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

405 410 415

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

420 425 430

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

435 440 445

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

450 455 460

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

465 470 475 480

Ser Leu Ser Pro Gly Lys

485

<210> 49

<211> 1461

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC EW

<400> 49

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

ggcggcggag gatctggcgg aggtggaagc ggaggcggtg gatctcccaa gagctgcgac 780

aagacccaca cctgtccccc ctgccctgcc cctgaactgc tgggcggacc cagcgtgttc 840

ctgttccccc caaagcccaa ggacaccctg atgatcagcc ggacccccga agtgacctgc 900

gtggtggtgg acgtgtccca cgaggaccct gaagtgaagt tcaattggta cgtggacggc 960

gtggaagtgc acaacgccaa gaccaagccc agagaggaac agtacaacag cacctaccgg 1020

gtggtgtccg tgctgaccgt gctgcaccag gactggctga acggcaaaga gtacaagtgc 1080

aaggtgtcca acaaggccct gcctgccccc atcgagaaaa ccatcagcaa ggccaagggc 1140

cagccccgcg agccccaggt gtacacactg ccccccagcc gggacgagct gaccgagaac 1200

caggtgtccc tgacctgcct ggtgaaaggc ttctacccca gcgatatcgc cgtggaatgg 1260

gagagcaacg gccagcccga gaacaactac aagaccaccc cccctgtgct ggacagcgac 1320

ggctcattct tcctgtacag ctggctgacc gtggacaaga gccggtggca gcagggcaac 1380

gtgttcagct gcagcgtgat gcacgaggcc ctgcacaacc actacaccca gaagtccctg 1440

agcctgagcc ccggcaagta g 1461

<210> 50

<211> 486

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC EW

<400> 50

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

245 250 255

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

260 265 270

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

275 280 285

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

290 295 300

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

305 310 315 320

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

325 330 335

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

340 345 350

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

355 360 365

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

370 375 380

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Glu Asn

385 390 395 400

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

405 410 415

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

420 425 430

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Trp

435 440 445

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

450 455 460

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

465 470 475 480

Ser Leu Ser Pro Gly Lys

485

<210> 51

<211> 1461

<212> DNA

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC RVT

<400> 51

gccaccatgt ggtggcgtct gtggtggctg ctgcttctgc tgttgctgct gtggcctatg 60

gtctgggcca tctcctacga cagccctgac tacaccgacg agtcctgcac cttcaagatc 120

tccctgcgga acttccggtc catcctgtcc tgggagctga agaaccactc catcgtgccc 180

acacactaca ccctgctgta caccatcatg tccaagcctg aggacctgaa ggtggtcaag 240

aactgcgcca acaccaccag atctttctgc gacctgaccg atgagtggcg gtctacccac 300

gaggcttacg tgacagtgct ggaaggcttc tccggcaata ccacactgtt cagctgctcc 360

cacaacttct ggctggccat cgacatgtcc ttcgagcctc cagagttcga gatcgtgggc 420

ttcaccaacc acatcaacgt gatggtcaag ttccccagca tcgtggaaga ggaactccag 480

ttcgacctga gcctggtcat cgaggaacag tccgagggca tcgtgaagaa gcacaagccc 540

gagatcaagg gcaacatgtc cggcaacttc acctacatca tcgacaagct gatccccaac 600

accaactact gcgtgtccgt gtacctggaa cactccgatg agcaggccgt gatcaagtcc 660

cctctgaagt gtaccctgct gcctcctggc caagagtctg agtctgccga gtctgctaaa 720

ggcggcggag gatctggcgg aggtggaagc ggaggcggtg gatctcccaa gagctgcgac 780

aagacccaca cctgtccccc ctgccctgcc cctgaactgc tgggcggacc cagcgtgttc 840

ctgttccccc caaagcccaa ggacaccctg atgatcagcc ggacccccga agtgacctgc 900

gtggtggtgg acgtgtccca cgaggaccct gaagtgaagt tcaattggta cgtggacggc 960

gtggaagtgc acaacgccaa gaccaagccc agagaggaac agtacaacag cacctaccgg 1020

gtggtgtccg tgctgaccgt gctgcaccag gactggctga acggcaaaga gtacaagtgc 1080

aaggtgtcca acaaggccct gcctgccccc atcgagaaaa ccatcagcaa ggccaagggc 1140

cagccccgcg agccccgggt gtacacactg ccccccagcc gggacgagct gaccaagaac 1200

caggtgtccc tgacctgcct ggtgaaaggc ttctacccca gcgatatcgc cgtggaatgg 1260

gagagcaacg gccagcccga gaacaactac aagaccaccc cccctgtgct ggtcagcgac 1320

ggctcattca ccctgtacag caagctgacc gtggacaaga gccggtggca gcagggcaac 1380

gtgttcagct gcagcgtgat gcacgaggcc ctgcacaacc actacaccca gaagtccctg 1440

agcctgagcc ccggcaagta g 1461

<210> 52

<211> 486

<212> PRT

<213> 人工序列

<220>

<223> IFNAR2-连接子_4GS*3-FC RVT

<400> 52

Ala Thr Met Trp Trp Arg Leu Trp Trp Leu Leu Leu Leu Leu Leu Leu

1 5 10 15

Leu Trp Pro Met Val Trp Ala Ile Ser Tyr Asp Ser Pro Asp Tyr Thr

20 25 30

Asp Glu Ser Cys Thr Phe Lys Ile Ser Leu Arg Asn Phe Arg Ser Ile

35 40 45

Leu Ser Trp Glu Leu Lys Asn His Ser Ile Val Pro Thr His Tyr Thr

50 55 60

Leu Leu Tyr Thr Ile Met Ser Lys Pro Glu Asp Leu Lys Val Val Lys

65 70 75 80

Asn Cys Ala Asn Thr Thr Arg Ser Phe Cys Asp Leu Thr Asp Glu Trp

85 90 95

Arg Ser Thr His Glu Ala Tyr Val Thr Val Leu Glu Gly Phe Ser Gly

100 105 110

Asn Thr Thr Leu Phe Ser Cys Ser His Asn Phe Trp Leu Ala Ile Asp

115 120 125

Met Ser Phe Glu Pro Pro Glu Phe Glu Ile Val Gly Phe Thr Asn His

130 135 140

Ile Asn Val Met Val Lys Phe Pro Ser Ile Val Glu Glu Glu Leu Gln

145 150 155 160

Phe Asp Leu Ser Leu Val Ile Glu Glu Gln Ser Glu Gly Ile Val Lys

165 170 175

Lys His Lys Pro Glu Ile Lys Gly Asn Met Ser Gly Asn Phe Thr Tyr

180 185 190

Ile Ile Asp Lys Leu Ile Pro Asn Thr Asn Tyr Cys Val Ser Val Tyr

195 200 205

Leu Glu His Ser Asp Glu Gln Ala Val Ile Lys Ser Pro Leu Lys Cys

210 215 220

Thr Leu Leu Pro Pro Gly Gln Glu Ser Glu Ser Ala Glu Ser Ala Lys

225 230 235 240

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Pro

245 250 255

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

260 265 270

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

275 280 285

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

290 295 300

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

305 310 315 320

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

325 330 335

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

340 345 350

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

355 360 365

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

370 375 380

Pro Arg Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

385 390 395 400

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

405 410 415

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

420 425 430

Thr Pro Pro Val Leu Val Ser Asp Gly Ser Phe Thr Leu Tyr Ser Lys

435 440 445

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

450 455 460

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

465 470 475 480

Ser Leu Ser Pro Gly Lys

485

<210> 53

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS

<400> 53

Gly Gly Gly Gly Ser

1 5

<210> 54

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*2

<400> 54

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10

<210> 55

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> 连接子_4GS*4

<400> 55

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

1 5 10 15

Gly Gly Gly Ser

20

<210> 56

<211> 6

<212> PRT

<213> 人工序列

<220>

<223> 连接子_6G

<400> 56

Gly Gly Gly Gly Gly Gly

1 5

<210> 57

<211> 8

<212> PRT

<213> 人工序列

<220>

<223> 连接子_8G

<400> 57

Gly Gly Gly Gly Gly Gly Gly Gly

1 5

<210> 58

<211> 12

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AEAAAKEAAAKA

<400> 58

Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala

1 5 10

<210> 59

<211> 46

<212> PRT

<213> 人工序列

<220>

<223> 连接子_EAAAK 复合物

<400> 59

Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys

1 5 10 15

Glu Ala Ala Ala Lys Ala Leu Glu Ala Glu Ala Ala Ala Lys Glu Ala

20 25 30

Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala

35 40 45

<210> 60

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> 连接子_EAAAK*3

<400> 60

Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys

1 5 10 15

<210> 61

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> 连接子_EAAAK

<400> 61

Glu Ala Ala Ala Lys

1 5

<210> 62

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> 连接子_EAAAK*2

<400> 62

Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys

1 5 10

<210> 63

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*5

<400> 63

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10

<210> 64

<211> 12

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*6

<400> 64

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10

<210> 65

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*7

<400> 65

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10

<210> 66

<211> 16

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*8

<400> 66

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

<210> 67

<211> 18

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*9

<400> 67

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro

<210> 68

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*10

<400> 68

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro

20

<210> 69

<211> 22

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*11

<400> 69

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro

20

<210> 70

<211> 24

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*12

<400> 70

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro

20

<210> 71

<211> 26

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*13

<400> 71

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

20 25

<210> 72

<211> 28

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*14

<400> 72

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

20 25

<210> 73

<211> 30

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*15

<400> 73

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

20 25 30

<210> 74

<211> 32

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*16

<400> 74

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

20 25 30

<210> 75

<211> 34

<212> PRT

<213> 人工序列

<220>

<223> 连接子_AP*17

<400> 75

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

1 5 10 15

Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro

20 25 30

Ala Pro

<210> 76

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> 连接子_PAPAP

<400> 76

Pro Ala Pro Ala Pro

1 5