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We found that life-stage had a greater impact on TCR\u03b2 and TCR\u03b1 gene segment usage than cell-type. Foetal repertoires showed bias towards 3\u2019TRAV and 5\u2019TRAJ rearrangements in all populations, whereas adult repertoires used more 5\u2019TRAV gene segments, suggesting that progressive TCR\u03b1 rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3\u2019TRAV and 5\u2019TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on \u03b1-chain and \u03b2-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCR\u03b2 repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing \u03b1\u03b2T-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.\n                  <\/jats:p>","DOI":"10.7554\/elife.93493","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T09:25:09Z","timestamp":1709630709000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.93493","source":"Crossref","is-referenced-by-count":6,"title":["Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-8528","authenticated-orcid":true,"given":"Jasmine","family":"Rowell","sequence":"first","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ching-In","family":"Lau","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health","place":["London, United 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