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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.<\/jats:p>","DOI":"10.1084\/jem.20201904","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T23:49:02Z","timestamp":1612828142000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["The thymoproteasome hardwires the TCR repertoire of CD8+ T cells in the cortex independent of negative selection"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-6957","authenticated-orcid":true,"given":"Izumi","family":"Ohigashi","sequence":"first","affiliation":[{"name":"Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan 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