Forces influencing the composition of the mature TCR repertoire have been well studied in the mouse. 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 Vβ 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 Vβ gene elements in CD45RO- CD4+ (naive) T cells versus CD45RO+ CD4+ (memory) T cells. A correlation between Vβ 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 HLDRB1 allele on the peripheral TCR repertoire. While the HLA-DRB1 imposed profile in Vβ distribution was maintained in CD45RO+ CD4+ T cells, it was less pronounced, indicating that antigenic experience modulates the functional TCR repertoire.
ASJC Scopus subject areas
- Immunology and Allergy