Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia.
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1485-90. doi: 10.1073/pnas.1323736111. Epub 2014 Jan 13.
The recall of memory CD8(+) cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual T-cell receptor (TCR) heterodimers, we characterized the antigen-driven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα- and β chain-dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity.
记忆性 CD8(+)细胞毒性 T 淋巴细胞（CTLs）的回忆，由先前的病毒感染或疫苗接种引发，对免疫保护至关重要。这种情况是由于随机克隆扩增还是特定克隆的主动选择尚不清楚。我们使用平行的过继转移方案结合单细胞分析来定义个体 T 细胞受体（TCR）异二聚体的互补决定区（CDR）3α和 CDR3β 区域，对三个个体受者中的相同记忆 CTL 群体的抗原驱动的回忆进行了表征。这种高分辨率分析显示，在所有受挑战的动物中，特定 TCR 克隆型的重现（或减少）具有可重复性。这些克隆组成的变化与 TCR 对病毒衍生肽（p）+主要组织相容性复合物 I 类分子的亲和力有关，并且与 TCRα 和 TCRβ 链有关。尽管存在这种指示差异选择的克隆型代表性变化，但没有证据表明整个库变窄，这表明在保护 TCR 多样性的同时优化 CTL 反应的策略。
