TCR repertoire: size, diversity, and function

National Institute On Aging

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Abstract

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.