TCR repertoire: size, diversity, and function

在胸腺T细胞发育过程中，通过V(D)J重组产生大量的T细胞受体(TCR)，涉及多个V、D和J基因的重排以及与链的配对。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体内癌细胞的侵袭。个体T细胞中存在的全部TCR被称为TCR谱系。尽管成人体内估计有4x1011个T细胞，但TCR谱系的下限估计为3.8x108。虽然循环T细胞的数量可能会随着年龄的增长而略有下降，但TCR谱系的多样性变化更为明显。在所有四个T细胞亚群中都观察到了TCR谱系随年龄的变化。初代CD8+T细胞减少最多，记忆性CD8+T细胞克隆性扩增最大，TCR序列保留率增加最多。我们的结果表明，与年龄相关的TCR谱系的磨损是CD8+T细胞亚群特有的，而且比CD4+T细胞更严重，这表明衰老对细胞毒作用的影响比对辅助T细胞功能的影响更深。这可能解释了老年人对新型感染的易感性增加的原因。

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.