Takase Mitsuyo, Kanagawa Edith M, Kanagawa Osami
RIKEN Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
J Immunol. 2007 Aug 15;179(4):2163-9. doi: 10.4049/jimmunol.179.4.2163.
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.
TCR与自身肽/MHC复合物之间的相互作用在成熟外周T细胞的稳态和抗原反应性中起重要作用。在本报告中，我们证明成熟外周T细胞与内源性抗原之间的相互作用以年龄依赖性方式对外源抗原特异性T细胞的维持产生负面影响。这是由RAG依赖性的TCRα链二次重排（受体修正）介导的。在将转基因TCRα链插入生理基因座的小鼠（敲入小鼠）中很容易观察到成熟T细胞中的TCR修正，而在具有相同TCRα链的传统转基因小鼠中则观察不到。因此，我们的结果表明，在所有TCRα链都易被二次重排删除的生理条件下，成熟外周T细胞中的TCR修正是成年动物中一个持续的过程，并导致T细胞功能和库的年龄依赖性变化。
