CN102295702B - 一种针对t细胞受体可变区特异性单抗的制备方法 - Google Patents
一种针对t细胞受体可变区特异性单抗的制备方法 Download PDFInfo
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Abstract
本发明公开了一种针对T细胞受体可变区特异性单抗的制备方法，首先制备可溶性T细胞受体蛋白，然后采用正反筛选获得可产特异性可变区单抗的杂交瘤株。应用本方法可以高效、快速的获得T细胞受体可变区特异性单抗，对设计和开发基于T细胞的相关疫苗和免疫治疗手段具有重要的意义。
Description
技术领域
本发明涉及一种单克隆抗体的制备方法，尤其是一种通过正反筛选法获得特异性单克隆抗体的方法。
背景技术
T细胞通过其表面T细胞受体（T cell receptor，TCR）识别主要组织相容性复合物分子（Major histocompatibility complex，MHC）呈递的多肽来行使其细胞功能，所以TCR的识别能力是T细胞行使功能的先决条件。与抗体分子一样，TCR组成链的形成也存在基因重排现象，即每条多肽链的编码基因都是由3个或4个基因片段组合而成。其中，短链α和γ是由可变区基因片段（V gene segment）、连接子基因片段（J gene segment）和恒定区基因片段（C gene segment）三种片段连接而成，而长链β和δ是由4个基因片段组合而成，包括与短链一样的3个基因片段和额外的多样性基因片段（D gene segment）。每个基因片段的相互连接处都存在核苷酸的随机缺失或增加，从而造成连接处的高度多样性。举例而言，人染色体上共含有42个Vα基因片段和46个Vβ基因片段，以及数目庞大的连接子基因片段Jα或Jβ，加上基因重排时基因片段连接处的高度多样性，就使得αβTCR库的数目高达1014个。我们知道，对于其他类型的细胞受体而言，没有一种细胞受体能和TCR一样具有如此多的多样性。所以我们可以想象，TCR与其配体之间的识别将比其他任何一种细胞受体都要复杂和奇妙。TCR主要通过其可变区的6个互补决定区域（Complementarity determining region，CDR）来与配体发生相互作用，所以可变区决定TCR的识别能力。而在病原抗原特异性或肿瘤抗原特异性的T细胞受体库研究中，我们往往会发现某些可变区基因片段会占优势，存在偏好性，而监测这些带有优势可变区基因片段的T细胞受体的变化情况对于我们设计和开发基于T细胞的相关疫苗和免疫治疗手段具有重要的意义。目前成熟应用的监测方法就是流式细胞仪技术，而要想应用流式细胞仪技术必然需要用到特异性的单克隆抗体。但是到目前为止，依然没有一种通用的方法来生产针对T细胞受体可变区特异性单克隆抗体的制备方法，本专利旨在提供一种能够有效生产该类单克隆抗体的方法，并申请保护。本发明通过体外复性技术获得可溶性T细胞受体蛋白，接着应用单克隆抗体杂交瘤技术生产单抗，并采用正反筛选法来获得某可变区特异性的单抗。
发明内容
本发明要解决的技术问题是提供一种针对T细胞受体可变区特异性单抗的制备方法。
为解决上述技术问题，本发明的技术方案为：首先制备可溶性T细胞受体蛋白，然后采用正反筛选获得可产特异性可变区单抗的杂交瘤株。
所述可溶性T细胞受体蛋白制备过程中通过引入人工二硫键稳定T细胞受体蛋白，所述人工二硫键由α链恒定区的T48–C和β链恒定区的S57–C组成。
为了更好的稳定T细胞受体蛋白，可同时将β链中的自由半胱氨酸突变成丙氨酸。
所述正反筛选的原理如下：T细胞受体胞外段由4个免疫球蛋白结构域组成，包括两个可变区和两个恒定区。所以当我们采用T细胞受体蛋白去免疫小鼠生产单抗时，我们得到的单抗有可能结合目标可变区外的其它三个结构域。为了高效获得目标可变区特异性的单抗，我们还要采用反筛法剔除那些不结合目标可变区的单抗。
其具体步骤如下：首先利用T细胞受体蛋白1免疫小鼠生产单抗，将能够结合T细胞受体1的单抗杂交瘤株留下；然后使用T细胞受体2筛选将第1）步获得的单抗杂交瘤株，将不能结合T细胞受体2的单抗杂交瘤株留下，得到可产特异性可变区1单抗的杂交瘤株；所述T细胞受体1与T细胞受体2的区别就在于目标可变区的不同，而其它三个结构域都相同。
应用本方法可以高效、快速的获得T细胞受体可变区特异性单抗，对设计和开发基于T细胞的相关疫苗和免疫治疗手段具有重要的意义。
附图说明
图1 单克隆抗体检测。
具体实施方式
实施例1 可溶性T细胞受体蛋白改造
以筛选Vδ1可变区（也叫TRDV1，TCR可变区信息请参考网站：http://www.imgt.org）的特异性单抗为例，我们来说明具体的实施方式。其中，我们用于正筛的T细胞受体1为S19-2，来源于HIV病人，识别的配体是HLA-A*2402限制性的nef138-10表位（来源于HIV病毒nef蛋白）。所有蛋白材料可由基因合成公司合成相应基因来表达。
HLA-A*2402的序列信息如SEQ ID NO.1所示，具体如下：
GSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDEETGKVKAHSQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW
Nef138-10表位多肽可由公司合成，其氨基酸序列如SEQ ID NO.2所示，具体如下：
为RYPLTFGWCF。
S19-2 TCR两条链的基因组成信息为：α链，TRDV1+TRAC；β链，TRBV30+TRBC。
α链蛋白序列如SEQ ID NO.3所示，具体如下：
MLFSSLLCVFVAFSYSGSSV AQKVTQAQSSVSMPVRKAVTLNCLYETSWWSYYIFWYKQLPSKEMIFLIRQGSDEQNAKSGRYSVNFKKAAKSVALTISALQLEDSAKYFCALGELARSGGYQKVTFGTGTKLQVIP NIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS CDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS
其中，带有下划线的部分为可变区序列，带有下划线且斜体字体部分为恒定区序列，位于可变区和恒定区之间的为高度可变的连接区序列。恒定区序列中的T48突变成C，用于后期的复性过程中可引入一对人工二硫键来稳定TCR蛋白的构象。
β链蛋白序列如SEQ ID NO.4所示，具体如下：
MLRSLLALLLGTFFGVRSQTIHQWPATLVQPVGSPLSLECTVEGTSNPNLYWYRQAAGRGLQLLFYSVGIGQISSEVPQNLSASRPQDRQFILSSKKLLLSDSGFYLCAWSVSVGAGVPTIYFGEGSWLTVV EDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD CGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF
其中，带有下划线的部分为可变区序列，带有下划线且斜体字体部分为恒定区序列，位于可变区和恒定区之间的为高度可变的连接区序列，恒定区之后的为跨膜区和胞内区序列。恒定区序列中的S57需要突变成C，用于后期的复性过程中可引入一对人工二硫键来稳定TCR蛋白的构象，同时将自由半胱氨酸C96突变成A，减少复性过程中多聚体的形成。
用于反筛法的T细胞受体2是在S19-2的基础上，将α链的可变区TRDV1替换成TRAV2-1，而β链保持不变，这个T细胞受体我们命名为S19-2-TRAV2-1。新组合而成的α链蛋白序列如SEQ ID NO.5所示，具体如下（仅包括可变区，连接区和恒定区序列）：
KEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVTLARSGGYQKVTFGTGTKLQVIP NIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS
将这三条多肽链构建到表达载体pET21a上，具体实验操作请见《分子克隆技术手册》。应用大肠杆菌E.coli表达系统表达包涵体蛋白并纯化，具体步骤如下：
1）将1-2 μL表达质粒转化到BL21（DE3）感受态细胞中，过夜，将单克隆菌落接种到40 mL LB培养基中，培养6-8小时。
2）每20 mL分别按照1%的接种量转接到含有2 L LB培养基的大摇瓶中，37℃培养至OD600=0.4-0.6，加入IPTG 至终浓度为1 mM，37℃继续培养5-6 小时。
3）收菌（以下步骤都在低温或冰水浴下进行），用60 mL左右1×PBS 悬浮，Φ6探头超声裂解（超声6 s，间隔12 s，99次，250 W，2个循环）。
4）17500 rpm，离心15 min。离心管下部呈白色致密块即为包涵体。
5）用移液器或玻璃棒小心的将包涵体上面一层细胞脆片吹打掉，弃上清。用Washing buffer悬浮。
6）超声，4 S，10 S，40 次，250 W。
7）重复步骤4-6，用Washing buffer 洗涤三次。
8）Resuspension buffer 悬浮，17500 rpm，离心15 min。
9） 除细胞碎片、弃上清，称重。按30mg/mL 的比例用包涵体溶解液（Disolution buffer）溶解，4℃搅拌过夜。
10）17500 rpm，20 min，取出上清或分装成1mL/管保存于-20℃或-80℃备用。
包涵体清洗液（Washing buffer）：0.5％ Triton-100，50 mM Tris pH 8.0，300 mM NaCl，10 mM EDTA，10 mM DTT(现用现加)；
包涵体重悬液(Rsuspension buffer)：50 mM Tris pH 8.0，100 mM NaCl，10 mM EDTA，10 mM DTT (现用现加)；
包涵体溶解液（Dissolution buffer）：6 M Gua-HCl（或8 M Urea），10％甘油，50mM Tris pH8.0，100 mM NaCl，10 mM EDTA，10 mM DTT(现用现加)；
实施例2 可溶性T细胞受体蛋白的复性
具体步骤如下：
1) 配制TCR复性液。一般为2 L，于冰上或4℃冷库预冷，复性过程在4℃冷库中进行。
2) 将盛有复性液的烧杯置于磁力搅拌器中，加入转子，设置合适的搅拌速度。这里以1sec转子转一圈为佳。找一个5 mL注射器换上1 mL的针头，将其固定在烧杯上。
3) α链和β链的包涵体按照2:1的质量比加入注射器(质量比例根据实际复性情况可进行调整)，即一次加入2 mL α链和1 mL β链，并混匀。使之一滴一滴的缓慢滴入复性液内，慢慢搅拌8小时。
4) 每隔8小时，重复一次步骤4，一共加三次包涵体，即一共加入6 mL的α链和3 mL β链。
5) 第三次加完包涵体后8小时，使用切向流仪器（TFF）进行浓缩，最后溶液体系为约300-400 mL，将浓缩后的蛋白复性溶液放入透析袋。
6) 复性液浓缩过程中，准备4 L 去离子水和4L 10 mM Tris缓冲液，4℃冷库预冷。
7) 先将装入透析袋的蛋白在水中透析24小时，再用10 mM Tris透析24小时，透析过程中需用转子搅拌。
8) 将透析后的蛋白液放入浓缩杯浓缩至100 mL。
9) 取出蛋白液，4℃，16, 000 rpm离心10分钟。取上清。
10) 用离子交换柱Source 15Q纯化，先分多次上样将蛋白结合到离子交换柱上，每次5ml，一般上满50 mL蛋白就洗脱一次，用盐浓度梯度洗脱，梯度一般为90分钟内从0% 拉到 50%。
11) 跑非还原和还原蛋白胶确定目的TCR蛋白峰，此后将所收集的蛋白用Superdex 200 柱子再次纯化。
复性液配方如下：
5M Urea
100mM Tris pH8.0
400mM L-Arg HCl （母液可配成2M）
2mM EDTA
5mM GSH （复性液预冷后再加入）
0.5mM GSSG（同上）
0.5mM PMSF （母液100mM，可不加）。
实施例3 正反筛选制备特异性单克隆抗体
T细胞受体胞外段由4个免疫球蛋白结构域组成，包括两个可变区和两个恒定区。所以当我们采用T细胞受体蛋白去免疫小鼠生产单抗时，我们得到的单抗有可能结合目标可变区外的其它三个结构域。为了高效获得目标可变区特异性的单抗，我们还要采用反筛法剔除那些不结合目标可变区的单抗。
所谓反筛法，首先需要我们应用体外复性技术构建一种用于反筛的T细胞受体蛋白2，同时为了方便陈述，我们将之前免疫小鼠的T细胞受体蛋白命名为T细胞受体1。T细胞受体1与T细胞受体2的区别就在于目标可变区的不同，而其它三个结构域都相同。
制备流程如下：
首先我们利用T细胞受体1免疫小鼠生产单抗，之后采用ELISA（酶联免疫吸附实验）技术来正反筛选所要的某可变区特异性单抗。第一步，正向筛选，将能够结合T细胞受体1的单抗杂交瘤株留下；第二步，在第一步获得的单抗杂交瘤株中，进一步用T细胞受体2反向筛选，即将不能结合T细胞受体2的单抗杂交瘤株留下，剔除那些能够与T细胞受体2结合的单抗杂交瘤株。经过这两步正反筛选获得的单抗杂交瘤株就是我们最后所要的某可变区特异性单抗。
还是以筛选Vδ1特异性单抗为例，我们通过实施例2里的方法获得可溶性T细胞受体1和T细胞受体2以后，进行上述的制备流程。结果我们共获得11株单抗杂交瘤株，采用ELISA实验进行验证。
操作步骤：
1）包被
用包被缓冲液将蛋白稀释至10ug/mL，每孔中加入0.1mL，先置37℃孵育2小时再转入4℃过夜。也可以将ELISA板直接置4℃过夜。
2）洗涤
包被结束后弃掉包被液，用PBST进行洗涤，方法为PBST加满每孔，静置5-10min，弃掉洗液，重新加满，重复洗涤3-5次，最后拍干ELISA板等待下一步封闭。
3）封闭
取第2步的ELISA板加10%小牛血清至每孔封闭，体积至少为所加包被液的两倍。封闭条件也有两种选择：直接置于4℃过夜，或者置于37℃温育2-4h。
4）洗涤
封闭结束的ELISA板进行洗涤，方法同步骤2。最后拍干等待加入一抗（单抗杂交瘤株培养细胞上清或小鼠腹水纯化单抗）。
5）加入一抗
一抗样品先用包被液稀释至所需浓度后加入到相应孔中。反应条件为37℃孵育2h。
6）洗涤
具体同步骤4。
7）加相应HRP-标记的商品化二抗
加相应的商品化HRP-标记的二抗，参考二抗说明书将二抗用封闭液稀释至适当倍数。将稀释好的二抗加入各孔，37℃反应1-1.5h。
8）洗涤
具体同步骤4。
9）显色
待步骤8完成后取100ulTMB底物显色液分加至ELISA各孔中。然后将ELISA板置于37℃反应约10min。
10）终止
将ELISA板取出，每孔加终止液（2mol/L硫酸溶液）终止反应，立即到酶标仪上读数，TMB为底物时波长为450nm。
试剂配制：
1）包被液（PH6.3的碳酸盐缓冲液）
无水Na2CO3 0.1696g
NaHCO3 0.2856g
无菌水 100ml
完全溶解至4℃,一周内使用
2）PBST配方
NaCl 8.0g
Na2HPO4.12H2O 2.9g
KCl 0.2g
KH2PO4 0.24g
TW-20 0.5ml
无菌水 1000ml
3）终止液
浓硫酸：无菌水 = 1:8
浓硫酸缓慢加入到无菌水 中，并搅拌散热。
最后我们获得ELISA数据如图1所示。结果显示其中10株都能特异性地结合Vδ1可变区，而有一株不能特异性地结合。所以应用我们的方法能够高效率的获得某可变区特异性单抗，并保证识别蛋白的活性构象表位，可用于流式细胞仪检测。
虽然本发明已以较佳实施例公开如上，但其并非用以限定本发明，任何熟悉此技术的人，在不脱离本发明的精神和范围内，都可做各种的改动与修饰，因此本发明的保护范围应该以权利要求书所界定的为准。
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<110> 中国科学院微生物研究所
<120> 一种针对T细胞受体可变区特异性单抗的制备方法
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Claims (4)
1.一种针对T细胞受体可变区特异性单抗的制备方法，其特征在于首先制备可溶性T细胞受体蛋白，然后采用正反筛选获得可产特异性可变区单抗的杂交瘤株；所示正反筛选包括如下步骤：
1）利用T细胞受体1免疫小鼠生产单抗，将能够结合T细胞受体1的单抗杂交瘤株留下；所述T细胞受体1为S19-2，识别的配体是HLA-A*2402限制性的nef138-10表位；HLA-A*2402的序列信息如SEQ ID NO.1所示；nef138-10氨基酸序列如SEQ ID NO.2所示；S19-2TCR两条链的基因组成信息为：α链，TRDV1+TRAC；β链，TRBV30+TRBC，α链蛋白序列如SEQ ID NO.3所示，β链蛋白序列如SEQ ID NO.4所示；
2）使用T细胞受体2筛选将第1）步获得的单抗杂交瘤株，将不能结合T细胞受体2的单抗杂交瘤株留下，得到特异性产T细胞受体可变区1单抗的杂交瘤株；所述T细胞受体2是在S19-2的基础上，将α链的可变区TRDV1替换成TRAV2-1，而β链保持不变；α链蛋白序列如SEQ ID NO.5所示。
2.权利要求1所述的方法，其特征在于所述可溶性T细胞受体蛋白中通过引入人工二硫键稳定T细胞受体蛋白。
3.权利要求2所述的方法，其特征在于所述人工二硫键由α链恒定区的第48位苏氨酸突变为半胱氨酸和β链恒定区的第57位丝氨酸突变为半胱氨酸组成。
4.权利要求2或3所述的方法，其特征在于还包括同时将β链中第96位的自由半胱氨酸突变成丙氨酸。
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1561343A (zh) * | 2001-08-31 | 2005-01-05 | 艾维德克斯有限公司 | 可溶性t细胞受体 |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0248887A4 (en) * | 1985-12-03 | 1990-01-08 | T Cell Sciences Inc | CELL-FREE T-CELL ANTIGUE RECEPTOR AND CLINICAL USE. |
| EP0616811A1 (en) * | 1985-12-03 | 1994-09-28 | T Cell Sciences, Inc. | Cell-free T cell antigen receptor and its clinical utilities |
| CN1561343A (zh) * | 2001-08-31 | 2005-01-05 | 艾维德克斯有限公司 | 可溶性t细胞受体 |
Non-Patent Citations (2)
| Title |
|---|
| Jun Liu et al.,."Revival of the identification of cytotoxic T-lymphocyte epitopes for immunological diagnosis，therapy and vaccine development".《Experimental Biology and Medicine》.2011,第236卷(第3期),第253页-第267页. |
| Jun Liu et al.,."Revival of the identification of cytotoxic T-lymphocyte epitopes for immunological diagnosis,therapy and vaccine development".《Experimental Biology and Medicine》.2011,第236卷(第3期),第253页-第267页. * |
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