T-CELL RECEPTOR V-SEGMENT FREQUENCIES IN PERIPHERAL-BLOOD T-CELLS CORRELATE WITH HUMAN-LEUKOCYTE ANTIGEN TYPE

We compared T cell receptor (TCR) V-segment frequencies in human leukocyte antigen (HLA) identical siblings to sibling pairs who differ at one or both HLA haplotypes using four V-beta-specific and one V-alpha-specific monoclonal antibody. In every one of nine families HLA-identical sibs had the most similar patterns of V-segment frequencies in their peripheral blood, whereas totally mismatched sibs were, in general, the most dissimilar; HLA haploidentical sibs tended to be intermediate between the two groups. The degree of similarity among HLA-identical sibs was comparable to that observed among three pairs of identical twins suggesting that HLA is the major genetic component influencing TCR V-segment frequency. Consistent with this observation, it was found that the frequency of T cells expressing particular V-beta-segments was skewed towards either CD4+ or CD8+ cells indicating that T cells expressing some V-beta-genes may be positively selected primarily by class I or class II major histocompatibility complex proteins. Finally, it was observed that individuals who express the HLA class I specificity, B38, tend to express high levels of V-alpha-2.3+ cells among their CD8+ T cells. These observations represent definitive proof that human V-segment frequencies are profoundly influenced by the HLA complex.