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In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced T cell receptor (TCR) sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity downregulate TCR sensitivity more slowly during positive selection, and associate membrane ion channel expression with thymocyte self-reactivity and progress through positive selection.<\/jats:p>","DOI":"10.7554\/elife.65435","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T08:15:15Z","timestamp":1619079315000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.65435","source":"Crossref","is-referenced-by-count":27,"title":["T cell self-reactivity during thymic development dictates the timing of positive selection"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6133-6294","authenticated-orcid":true,"given":"Lydia K","family":"Lutes","sequence":"first","affiliation":[{"name":"Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United 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