Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals.
Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals.
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DOI：
10.1038/s41598-017-03855-x
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Ichinohe T
中科院分区：
文献类型：
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作者：
Miyama T;Kawase T;Kitaura K;Chishaki R;Shibata M;Oshima K;Hamana H;Kishi H;Muraguchi A;Kuzushima K;Saji H;Shin-I T;Suzuki R;Ichinohe T
为了扩展我们对抗原特异性T细胞亚群的T细胞受体（TCR）库的个体发育的了解，我们结合了下一代深度测序和单细胞多重克隆型分析来评估配对TCR的多样性和频率、它们的功能以及克隆型TCR是否在不同个体之间共享。使用HLA-A*02限制性巨细胞病毒（CMV）pp 65衍生的免疫原性肽，我们发现健康供体血液中更占优势的pp 65特异性TCR克隆型对CMV肽具有更高的结合亲和力，并且来自个体之间高度共享的克隆型。有趣的是，这些高度共享的HLA-A*02限制性CMV特异性TCR在CMV血清阴性个体以及HLA-A*02阴性供体中检测到，尽管频率较低。更有趣的是，这些共享的TCR克隆型在干记忆T细胞亚群中是丰富的，并且干记忆T细胞库的TCR多样性显著低于中央记忆和效应记忆T细胞库。这些结果表明，干细胞记忆T细胞亚群可以作为高度共享和高功能记忆T细胞的水库。
To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.