The thymoproteasome hardwires the TCR repertoire of CD8+ T cells in the cortex independent of negative selection

The thymoproteasome expressed specifically in thymic cortical epithelium optimizes the generation of CD8+ T cells. However, how the thymoproteasome contributes to CD8+ T cell development is unclear. Here we show that the thymoproteasome shapes the TCR repertoire directly in cortical thymocytes before migration to the thymic medulla. We further show that the thymoproteasome optimizes CD8+ T cell production independent of the thymic medulla, independent of additional antigen-presenting cells including medullary thymic epithelial cells and dendritic cells, and independent of apoptosis-mediated negative selection. These results indicate that the thymoproteasome hardwires the TCR repertoire of CD8+ T cells with cortical positive selection independent of negative selection in the thymus. Single cell 5' RNA-Seq on thymocyte subpopulations from Beta5t-deficient I-A-deficient and control I-A-deficient mice.