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Immunol."],"abstract":"<jats:p>V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the <jats:italic>Tcra<\/jats:italic> gene occurs in CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> double positive (DP) thymocytes and requires the <jats:italic>Tcra<\/jats:italic> enhancer (E\u03b1). E proteins are known regulators of DP thymocyte development and have three identified binding sites in E\u03b1. To understand the contribution of E proteins to E\u03b1 function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of \u03b1\u03b2 T cell development. Further investigation revealed loss of germline transcription within the <jats:italic>Tcra<\/jats:italic> locus at the J\u03b1 array, along with dysregulated primary and impaired secondary V\u03b1-J\u03b1 rearrangement. E\u03b1 E protein binding increases <jats:italic>Tcra<\/jats:italic> locus accessibility and regulates TCR\u03b1 recombination, thus directly promoting <jats:italic>Tcra<\/jats:italic> repertoire diversity.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1188738","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T15:11:55Z","timestamp":1688656315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["E protein binding at the Tcra enhancer promotes Tcra repertoire diversity"],"prefix":"10.3389","volume":"14","author":[{"given":"Ariana","family":"Mihai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumedha","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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