Influence of HLA genes on T cell receptor V segment frequencies and expression levels in peripheral blood lymphocytes.

The effect of the HLA complex on the TCR repertoire in human peripheral blood was assessed by using nine V beta- and V alpha-specific mAb and the quantitative polymerase chain reaction specific for 22 V beta segments. Studies in randomly selected and unrelated individuals failed to show any influence of the HLA complex on the TCR repertoire. In contrast, studies in large families with multiple siblings showed a strong influence on the TCR repertoire by the HLA complex. In pairwise comparisons, HLA-identical sibs had more similar patterns of V segment frequencies, as measured with the nine V segment-specific mAb, as well as more similar expression levels of V beta-specific RNA, as measured by quantitative polymerase chain reaction, than totally mismatched or haplo-identical sibs. When the amount of V beta-specific RNA expressed in CD4+ and CD8+ T cells was compared, it was found that V beta 2, 5.1, 9, and 20 were skewed toward CD4+ T cells; on the other hand, V beta 7 and 14 showed a bias in expression for CD8+ T cells, suggesting that the former were positively selected predominantly by HLA class II gene products whereas the latter V beta segments were positively selected predominantly by HLA class I gene products. These studies unequivocally document the effects of HLA genes on TCR V segment frequencies and expression levels in peripheral blood T lymphocytes.