Endocrine Abstracts

During the development in the thymus, a virgin repertoire of diverse TCR-αβ recognition specificities in immature T cells is selected through positive and negative selection to form a functionally competent and self-tolerant repertoire of mature T cells. Positive selection supports the survival of self-MHC-restricted thymocytes that receive low-affinity TCR engagement, whereas negative selection deletes potentially harmful self-reactive thymocytes upon high-affinity TCR engagement. Recent advances in the biology of thymic stromal cells have indicated that proximal interplays among developing T cells, dendritic cells, and thymic medullary epithelial cells that promiscuously express tissue-specific self-antigens is essential for the establishment of a self-tolerant TCR repertoire. It has also been indicated that the formation of an immunocompetent TCR repertoire requires positive selection by thymic cortical epithelial cells that express unique protein degradation machineries, including the β5t-containing thymoproteasome. These results suggest an essential role of self-peptide repertoires specifically expressed by multiple thymic microenvironments in the development of an immunocompetent and self-tolerant T cell repertoire.

Declaration of funding

This work was supported by grants-in-aid for Scientific Research from MEXT and JSPS (grant numbers 23249025 and 24111004).