Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells.
Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells.
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DOI：
10.1126/scitranslmed.aaf1278
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发表时间：
2016-06-01
影响因子：
17.1
通讯作者：
Jiang N
中科院分区：
文献类型：
--
作者：
Zhang SQ;Parker P;Ma KY;He C;Shi Q;Cui Z;Williams CM;Wendel BS;Meriwether AI;Salazar MA;Jiang N
T细胞识别和杀死无数的病原体感染或癌细胞使用不同的T细胞受体（TCR）。TCR对同源抗原的亲和力在过继性T细胞转移免疫疗法和抗原特异性T细胞库免疫谱分析中具有高度兴趣，因为众所周知其与下游T细胞应答相关。在这里，我们介绍了原位TCR亲和力和序列测试（iTAST），用于同时测量人血液中单个原代CD8+ T细胞的TCR亲和力和序列。我们证明了来自病原体缺乏经验的个体的初级抗原特异性T细胞的库具有由不同TCR序列组成的1000倍的令人惊讶的广泛亲和力范围。在此范围内，与年轻个体相比，来自老年个体的样品含有降低频率的高亲和力T细胞，这表明T细胞磨损的年龄相关效应可能导致库中的漏洞。iTAST应该能够离体快速选择用于过继免疫治疗的高亲和力TCR和用于免疫监测应用的T细胞应答的测量。
T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCR). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. Here, we introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8+ T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications.
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DOI：
10.4049/jimmunol.1401717
发表时间：
2015-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nakatsugawa M;Yamashita Y;Ochi T;Tanaka S;Chamoto K;Guo T;Butler MO;Hirano N
通讯作者：
Hirano N
影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
Davis, Mark M.
DOI：
10.1038/nri3191
发表时间：
2012-03-22
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Restifo NP;Dudley ME;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
3.4
作者：
Chesla, SE;Selvaraj, P;Zhu, C
通讯作者：
Zhu, C
影响因子：
48
作者：
Shugay, Mikhail;Britanova, Olga V.;Chudakov, Dmitriy M.
通讯作者：
Chudakov, Dmitriy M.