TCR repertoire: size, diversity, and function

在胸腺中T细胞发育期间通过V（D）J重组产生大量T细胞受体（TCR），所述重组涉及多个V、D和J基因的重排以及和链的配对。这些不同的TCR为人体提供保护，使其免受多种外来病原体和内部癌细胞的侵害。存在于个体T细胞中的全部TCR被称为TCR库。尽管成人体内估计有4 × 1011个T细胞，但TCR库的下限估计值为3.8 × 108。虽然循环T细胞的数量可能会随着年龄的增长而略有减少，但TCR库的多样性变化更为明显。在所有四个T细胞亚群中观察到TCR库随年龄的变化。在初始CD8 + T细胞中观察到最大的减少;在记忆性CD8 + T细胞中观察到最大的克隆扩增，并且在记忆性CD8 + T细胞中观察到最高的TCR序列保留增加。我们的研究结果表明，年龄相关的TCR库磨损是亚群特异性的，并且对CD8 + T细胞比CD4 + T细胞更深刻，这表明衰老对细胞毒性T细胞功能的影响比对辅助性T细胞功能的影响更深刻。这可能解释了老年人对新感染的易感性增加。

A vast array of T cell receptors (TCRs) is generated during T cell development in the thymus through V(D)J recombination, which involves the rearrangement of multiple V, D, and J genes and the pairing of and chains. These diverse TCRs provide protection to the human body against a multitude of foreign pathogens and internal cancer cells. The entirety of TCRs present in an individual's T cells is referred to as the TCR repertoire. Despite an estimated 4 x 1011 T cells in the adult human body, the lower bound estimate for the TCR repertoire is 3.8 x 108. While the number of circulating T cells may slightly decrease with age, the changes in the diversity of the TCR repertoire is more apparent. Alterations of TCR repertoire with age were observed in all four subsets of T cells. The greatest reduction was observed in nave CD8+ T cells; the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting aging has a more profound impact on the cytotoxic than on the helper T cell functions. This may explain the increased susceptibility of older adults to the novel infections.