DO HLA GENES PLAY A PROMINENT ROLE IN DETERMINING T-CELL RECEPTOR V-ALPHA SEGMENT USAGE IN HUMANS

Previous studies in humans have demonstrated that HLA genes can profou ndly influence the TCR V beta repertoire. To similarly assess the infl uence of HLA genes on the TCR V alpha segment repertoire, the V alpha repertoires of 12 individuals from three unrelated families were deter mined by quantitative PCR. Each family contained at least one pair of HLA-identical and -nonidentical siblings. Repertoire analysis was perf ormed on purified CD4(+) and CD8(+) cells by using V alpha-specific pr imers. We were unable to demonstrate more similar V alpha repertoires between HLA-identical siblings than between HLA-nonidentical siblings. In contract, when a similar analysis was performed on the same indivi duals for the V beta repertoire, HLA-identical siblings were found to have significantly more similar repertoires than HLA-nonidentical sibl ings. Furthermore, both the V alpha and V beta repertoires of monozygo tic twins showed striking similarity, Despite our inability to show an influence of HLA genes on the V alpha repertoire, we did observe a ve ry strong skewing in terms of preferential expression on CD4(+) or CD8 (+) cells of several V alpha segments, notably TCRAV1, -2, -5, -6, -7, -11, -12, and -13. These studies suggest that HLA genes play less of a role in determining V alpha segment usage than V beta. Nevertheless, the pronounced skewing of V alpha segment expression in the CD4(+) or CD8(+) populations suggests some role for HLA genes in determining th e V alpha TCR repertoire. Furthermore, the striking similarity of V al pha repertoires of identical twins suggests a major role for non-HLA g enes in determining the V alpha repertoire.