Thymoproteasome optimizes positive selection of CD8⁺ T cells without contribution of negative selection

Functionally competent and self-tolerant T cell repertoire is shaped through positive and negative selection in the cortical and medullary microenvironments of the thymus. The thymoproteasome specifically expressed in the cortical thymic epithelium is essential for the optimal generation of CD8⁺ T cells. Although how the thymoproteasome governs the generation of CD8⁺ T cells is not fully understood, accumulating evidence suggests that the thymoproteasome optimizes CD8⁺ T cell production through the processing of self-peptides associated with MHC class I molecules expressed by cortical thymic epithelial cells. In this review, we describe recent advances in the mechanism of thymoproteasome-dependent generation of CD8⁺ T cells, focusing on the process of cortical positive selection independent of apoptosis-mediated negative selection.