Skewed TCRVβ repertoire in human thymus persists after thymic emigration:: Influence of genomic imposition, thymic maturation and environmental challenge on human TCRVβ usage in vivo

In order to investigate the mechanisms involved in originating a diverse TCR repertoire in human peripheral blood we analyzed TCRV beta surface expression in different T cell subsets of unrelated individuals. The relative frequencies of 11 distinct V beta chains were determined for immature double positive (DP) as well as for mature CD4 single positive (4SP) and CD8 single positive (8SP) thymocytes, respectively. By comparing these data with expression in peripheral blood T lymphocytes of the same donors we were able to show that usage of TCRV beta in peripheral T cells is significantly (p < 0.001) depending on the pattern in mature SP thymocytes whereas the frequency of TCRV beta families in immature DIS thymocytes has no impact (p > 0.2). No association with distinct HLA-haplotypes was observed. Preferential usage of VP-families in either CD4- or CD8-positive peripheral T cells also correlates with the status in mature thymic precursors (p < 0.001). Altogether, this first combined study of TCR frequencies within different stages of human T cell ontogeny indicates that TCRV beta repertoire is determined mainly through selectional processes within the thymus. Since neither genomically imposed expression nor modulating events in the periphery seem to have strong influence on the relative expression of TCRV beta chains these findings have to be considered in future studies of human diseases.