Age-dependent TCR revision mediated by interaction between alphabeta TCR and self-antigens.
Interactions between TCR and self-peptide/MHC complex play an important role in homeostasis and Ag reactivity of mature peripheral T cells. In this report, we demonstrate that the interactions between mature peripheral T cells and endogenous Ags have a negative impact on the maintenance of foreign Ag-specific T cells in an age-dependent manner. This is mediated by RAG-dependent secondary rearrangement of the TCR alpha-chain (receptor revision). The TCR revision in mature T cells is readily observed in mouse expressing transgenic TCR alpha-chain inserted into the physiological locus (knockin mouse) but not in conventional transgenic mouse with an identical TCR alpha-chain. Thus, our results suggest that under physiological conditions in which all TCR alpha-chains are susceptible to deletion by secondary rearrangement, TCR revision in mature peripheral T cells is an ongoing process in adult animals and contributes to age-dependent changes in T cell function and repertoire.
Takase
Mitsuyo
M
RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
Kanagawa
Edith M
EM
Kanagawa
Osami
O
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D040641:Quantitative Trait Loci / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D006649:Histocompatibility Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta