HLA-DRB1 molecules and antigenic experience shape the repertoire of CD4 T cells

Forces influencing the composition of the mature TCR repertoire have been well studied in the mouser In particular, the contribution of MHC molecules in negative and positive selection events of T lymphocytes has been established. To understand whether the allelic polymorphism of HLA-DRB1 molecules can shape the human TCR repertoire, we compared the usage of TCR V beta segments in two cohorts of unrelated individuals who were selected for the expression of HLA-DRB1 alleles. To investigate the potential role of antigenic experience in shaping the TCR repertoire, we compared the usage of vp gene elements in CD45RO(-) CD4(+) (naive) T cells versus CD45RO(+) CD4(+) (memory) T cells. A correlation between V beta gene segment usage and HLA-DRB1 alleles could be demonstrated for the repertoire of the naive CD4(+) T cells, suggesting a shaping force of the HLA-DRB1 allele on the peripheral TCR repertoire. While the HLA-DRB1 imposed profile in V beta distribution was maintained in CD45RO(+) CD4(+) T cells, it was less pronounced, indicating that antigenic experience modulates the functional TCR repertoire.