Contribution of TCR-beta locus and HLA to the shape of the mature human Vbeta repertoire

T cells that survive thymic selection express a diverse array of unique heterodimeric αβ TCRs that mediate peptide-MHC Ag recognition. The proportion of the total T cell repertoire that expresses a particular Vβ protein may be determined by a variety of factors: 1) germline preference for use of particular Vβ genes; 2) allelic effects on the expression of different Vβ genes; and 3) HLA effects on the expression of different Vβ genes (acting via thymic selection and/or peripheral mechanisms). In this study, we show that Vβ usage by human CD4+ and CD8+ T cells in neonatal and adult donors is highly correlated between unrelated individuals, suggesting that a large proportion of the observed pattern of Vβ expression is determined by factors intrinsic to the TCR-β locus. The presence of identical TCR alleles (within an individual) leads to a significantly better correlation between CD4+ and CD8+ T cells with respect to Vβ expression; these effects are, however, relatively minor. The sharing of HLA alleles between individuals also leads to an increased correlation between their Vβ expression patterns, although this did not reach statistical significance. We therefore conclude that the correlation in Vβ expression patterns between CD4+ and CD8+ T cells can be explained predominantly by germline TCR-β locus factors and not TCR-β allelic or HLA effects