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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:p>\n                    During normal T cell development in mouse and human, a low-frequency population of immature CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double-negative (DN) thymocytes expresses early, mature \u03b1\u03b2 T cell antigen receptor (TCR). We report that these early \u03b1\u03b2 TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3\u03b4 but not major histocompatibility complex (MHC) for their generation\/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional \u03b1\u03b2 T cells. We found these data to be connected with observations that EADN cells were susceptible to T cell acute lymphoblastic leukemia (T-ALL) transformation in both humans and mice. Using the OT-1 TCR transgenic system to model EADN-stage \u03b1\u03b2 TCR expression, we found that EADN leukemogenesis required MHC to induce development of T-ALL bearing NOTCH1 mutations. This leukemia-driving MHC requirement could be lost, however, upon passaging the tumors in\u00a0vivo, even when matching MHC was continuously present in recipient animals and on the tumor cells themselves. These data demonstrate that MHC:TCR signaling can be required to initiate a cancer phenotype from an understudied developmental state that appears to be represented in the mouse and human disease spectrum.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2118529119","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T13:54:56Z","timestamp":1656510896000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Early expression of mature \u03b1\u03b2 TCR in CD4\n                    <sup>\u2212<\/sup>\n                    CD8\n                    <sup>\u2212<\/sup>\n                    T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7322-9875","authenticated-orcid":false,"given":"Kimberly G.","family":"Laffey","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology &amp; 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