Age-Dependent TCR Revision Mediated by Interaction between αβ TCR and Self-Antigens

Abstract

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 α-chain (receptor revision). The TCR revision in mature T cells is readily observed in mouse expressing transgenic TCR α-chain inserted into the physiological locus (knockin mouse) but not in conventional transgenic mouse with an identical TCR α-chain. Thus, our results suggest that under physiological conditions in which all TCR α-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.