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  • Title: Do HLA genes play a prominent role in determining T cell receptor V alpha segment usage in humans?
    Author: Gulwani-Akolkar B, Shi B, Akolkar PN, Ito K, Bias WB, Silver J.
    Journal: J Immunol; 1995 Apr 15; 154(8):3843-51. PubMed ID: 7706724.
    Abstract:
    Previous studies in humans have demonstrated that HLA genes can profoundly influence the TCR V beta repertoire. To similarly assess the influence of HLA genes on the TCR V alpha segment repertoire, the V alpha repertoires of 12 individuals from three unrelated families were determined by quantitative PCR. Each family contained at least one pair of HLA-identical and -nonidentical siblings. Repertoire analysis was performed on purified CD4+ and CD8+ cells by using V alpha-specific primers. We were unable to demonstrate more similar V alpha repertoires between HLA-identical siblings than between HLA-nonidentical siblings. In contrast, when a similar analysis was performed on the same individuals for the V beta repertoire, HLA-identical siblings were found to have significantly more similar repertoires than HLA-nonidentical siblings. Furthermore, both the V alpha and V beta repertoires of monozygotic twins showed striking similarity. Despite our inability to show an influence of HLA genes on the V alpha repertoire, we did observe a very 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 the V alpha TCR repertoire. Furthermore, the striking similarity of V alpha repertoires of identical twins suggests a major role for non-HLA genes in determining the V alpha repertoire.
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