{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:03:07Z","timestamp":1793350987250,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32CA009138"],"award-info":[{"award-number":["T32CA009138"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Thymocyte maturation is a tightly controlled and sequential process of T cell receptor (TCR) gene rearrangement that generates a broad repertoire of T cells with minimal self-reactivity. We previously generated TCR exchange (TRex) mice by targeting a mesothelin-specific \u201c1045\u201d TCR to the Trac locus in murine zygotes. While 1045\u2009T cells from TRex mice display physiological development and function, some T cells coexpress endogenous TCR\u03b2 chains, suggesting that \u03b2-selection is required for 1045\u2009T cell development. Here, we evaluate thymocyte maturation in the setting of compromised \u03b2-selection by deleting endogenous Tcrb or Rag2 in TRex mice. T cells readily form in TRex mice lacking Tcrb, though thymocytes mature through developmental trajectories that appear dependent on interleukin-7 and \u03b3\u03b4TCR. In contrast, mature T cells fail to form in the absence of Rag2. Maturation of \u03b1\u03b2 thymocytes bypassing \u03b2-selection is reduced by 100-fold, in part because \u03b3\u03b4TCR+ precursors are biased to form conventional \u03b3\u03b4 T cells. Nevertheless, in TRex mice, these unconventional \u03b2-selection\u2013independent trajectories yield a mature \u03b1\u03b2 T cell population with uniform TCR expression and pronounced function.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf035","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T21:20:25Z","timestamp":1752614425000},"source":"Crossref","is-referenced-by-count":3,"title":["Maturation of thymocytes with a monoclonal TCR under control of <i>Trac<\/i> promoter elements in the absence of \u03b2-selection"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-1946","authenticated-orcid":false,"given":"Alexander K","family":"Tsai","sequence":"first","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Cruz-Hinojoza","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline A","family":"Ellefson","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L","family":"Burrack","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M","family":"Larsen","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingunn M","family":"Stromnes","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]},{"name":"Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"2025071517202175700_vlaf035-B1","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.4049\/jimmunol.149.7.2281","article-title":"Phenotypic and functional characterization of c-kit expression during intrathymic T cell 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Rev"},{"key":"2025071517202175700_vlaf035-B5","doi-asserted-by":"crossref","first-page":"eadh4059","DOI":"10.1126\/science.adh4059","article-title":"The immunopathological landscape of human pre-TCR\u03b1 deficiency: From rare to common variants","volume":"383","author":"Materna","year":"2024","journal-title":"Science"},{"key":"2025071517202175700_vlaf035-B6","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.4049\/jimmunol.152.10.4783","article-title":"Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation","volume":"152","author":"Godfrey","year":"1994","journal-title":"J Immunol"},{"key":"2025071517202175700_vlaf035-B7","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/intimm\/9.10.1475","article-title":"Pre-TCR signaling components trigger transcriptional activation of a rearranged TCR alpha gene locus and silencing of the pre-TCR alpha locus: implications for intrathymic differentiation","volume":"9","author":"Koyasu","year":"1997","journal-title":"Int Immunol"},{"key":"2025071517202175700_vlaf035-B8","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.it.2021.06.005","article-title":"New insights into TCR \u03b2-selection","volume":"42","author":"Dutta","year":"2021","journal-title":"Trends Immunol"},{"key":"2025071517202175700_vlaf035-B9","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"2025071517202175700_vlaf035-B10","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1002\/j.1460-2075.1995.tb00146.x","article-title":"Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene","volume":"14","author":"Malissen","year":"1995","journal-title":"EMBO 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genetically modified mice","volume":"154","author":"P\u00e9nit","year":"1995","journal-title":"J Immunol"},{"key":"2025071517202175700_vlaf035-B44","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.4049\/jimmunol.163.11.6053","article-title":"TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement","volume":"163","author":"Mancini","year":"1999","journal-title":"J Immunol"},{"key":"2025071517202175700_vlaf035-B45","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0092-8674(00)80291-3","article-title":"Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice","volume":"89","author":"Akashi","year":"1997","journal-title":"Cell"},{"key":"2025071517202175700_vlaf035-B46","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1074-7613(00)80329-5","article-title":"Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain 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