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

Mitsuyo Takase^*, Edith M. Kanagawa and Osami Kanagawa^1,*

^* RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan; and Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, MO 63110

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

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¹ Address correspondence and reprint requests to Dr. Osami Kanagawa, RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan. E-mail address: kanagawa{at}rcai.riken.jp

² Abbreviations used in this paper: ES, embryonic stem; KI, knockin; TG, transgenic.