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During their ontogeny, iNKT cells differentiate into discrete iNKT1, iNKT2, and iNKT17 effector subsets akin to helper CD4 T cells. In this study, we found that transgenic (Tg) expression of the canonical V\u03b114-J\u03b118 TCR\u03b1-chain at the double-positive thymocyte stage led to premature iNKT cell development and a cell-intrinsic bias toward iNKT2 cells, due to increased TCR signaling upon selection. Consistent with the strong iNKT2 bias, innate memory CD8+ T cells were found in greater numbers in V\u03b114 Tg mice, whereas the prevalence of mucosa-associated invariant T cells was reduced. iNKT cells from V\u03b114 Tg mice were hyporesponsive to stimulation by their cognate Ag \u03b1-galactosylceramide. Finally, V\u03b114 Tg mice displayed increased B16F10 melanoma tumor growth compared with wild-type mice. This study reveals some of the limitations of V\u03b114 Tg mice and warrants the cautious interpretation of past and future findings using this mouse model.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000100","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T22:14:10Z","timestamp":1608156850000},"page":"797-808","source":"Crossref","is-referenced-by-count":4,"title":["Altered Innate-like T Cell Development in V\u03b114-J\u03b118 TCR\u03b1 Transgenic Mice"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-0080","authenticated-orcid":false,"given":"Irene","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-6590","authenticated-orcid":false,"given":"Carolina","family":"de Amat Herbozo","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meggie","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaochu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Paget","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019\u00c9tude des Pathologies Respiratoires, UMR1100, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Tours , 37012 Tours ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Mallevaey","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]},{"name":"Institute of Biomedical Engineering, University of Toronto , Toronto, Ontario M5S 3G9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"2025010608425302700_r1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41577-018-0034-2","article-title":"Tissue-specific functions of invariant natural killer T cells","volume":"18","author":"Crosby","year":"2018","journal-title":"Nat. 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