HLA-DRB1 MOLECULES AND ANTIGENIC EXPERIENCE SHAPE THE REPERTOIRE OF CD4 T-CELLS

Forces influencing the composition of the mature TCR repertoire have b een well studied in the mouser In particular, the contribution of MHC molecules in negative and positive selection events of T lymphocytes h as been established. To understand whether the allelic polymorphism of HLA-DRB1 molecules can shape the human TCR repertoire, we compared th e usage of TCR V beta segments in two cohorts of unrelated individuals who were selected for the expression of HLA-DRB1 alleles. To investig ate the potential role of antigenic experience in shaping the TCR repe rtoire, we compared the usage of vp gene elements in CD45RO(-) CD4(+) (naive) T cells versus CD45RO(+) CD4(+) (memory) T cells. A correlatio n between V beta gene segment usage and HLA-DRB1 alleles could be demo nstrated 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 maintai ned in CD45RO(+) CD4(+) T cells, it was less pronounced, indicating th at antigenic experience modulates the functional TCR repertoire.