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A prominent example is the human phosphoantigen\u2010reactive V\u03b39V\u03b42 T cell subset that is absent in mice. Murine \u03b3\u03b4 thymocyte cells were among the first immune cells identified to follow a wave\u2010based layered development during embryonic and early life, and since this initial observation, in\u2010depth insight has been obtained in their thymic ontogeny. By contrast, less is known about the development of human \u03b3\u03b4 T cells, especially regarding the generation of \u03b3\u03b4 thymocyte waves. Here, after providing an overview of thymic \u03b3\u03b4 wave generation in several vertebrate classes, we review the evidence for \u03b3\u03b4 waves in the human fetal thymus, where single\u2010cell technologies have allowed the breakdown of human \u03b3\u03b4 thymocytes into functional waves with important TCR associations. Finally, we discuss the possible mechanisms contributing to the generation of waves of \u03b3\u03b4 thymocytes and their possible significance in the periphery.<\/jats:p>","DOI":"10.1111\/imr.13184","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T06:15:17Z","timestamp":1673331317000},"page":"89-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Surfing on the waves of the human \u03b3\u03b4 T cell ontogenic sea"],"prefix":"10.1111","volume":"315","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-1748","authenticated-orcid":false,"given":"Guillem","family":"Sanchez\u00a0Sanchez","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"},{"name":"Institute for Medical Immunology Universit\u00e9 Libre de Bruxelles (ULB)  Gosselies Belgium"},{"name":"ULB Center for Research in Immunology (U\u2010CRI) Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"},{"name":"WELBIO Department WEL Research Institute  Wavre Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-6244","authenticated-orcid":false,"given":"Yohannes","family":"Tafesse","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"},{"name":"Institute for Medical Immunology Universit\u00e9 Libre de Bruxelles (ULB)  Gosselies Belgium"},{"name":"ULB Center for Research in Immunology (U\u2010CRI) Universit\u00e9 Libre de Bruxelles (ULB)  Brussels Belgium"},{"name":"WELBIO Department WEL Research Institute  Wavre 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