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 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 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 V beta 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.
Walser-Kuntz
D R
DR
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Weyand
C M
CM
Fulbright
J W
JW
Moore
S B
SB
Goronzy
J J
JJ
D000483:Alleles; D000940:Antigenic Variation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens