{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:00:22Z","timestamp":1791284422126,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire. The increased binding strength of the TCR repertoire for self-pMHC in neonates was not solely due to reported defects in clonal deletion. Rather, our data suggest that thymic selection is altered in young mice such that thymocytes bearing TCRs with low affinity for self-peptide are not efficiently selected into the neonatal repertoire, and stronger TCR signals accompany both conventional and regulatory T cell selection. Importantly, the distinct levels of T cell self-reactivity reflect physiologically relevant differences based on the preferential expansion of T cells from young mice to fill a lymphopenic environment. Therefore, differences in thymic selection in young versus adult mice skew the TCR repertoire, and the relatively higher self-reactivity of the T cell pool may contribute to the distinct immune responses observed in neonates.<\/jats:p>","DOI":"10.4049\/jimmunol.1602137","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T00:30:22Z","timestamp":1498696222000},"page":"965-973","source":"Crossref","is-referenced-by-count":53,"title":["Alterations in the Thymic Selection Threshold Skew the Self-Reactivity of the TCR Repertoire in Neonates"],"prefix":"10.1093","volume":"199","author":[{"given":"Mengqi","family":"Dong","sequence":"first","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4,","place":["Canada"]},{"name":"Department of Microbiology, Infectious Diseases, and Immunology, University of Montreal , Montreal, Quebec H3T 1J4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Artusa","sequence":"additional","affiliation":[{"name":"Department of Physiology and McGill Research Centre for Complex Traits, McGill University , Montreal, Quebec H3G 1Y6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Alberta , Edmonton, Alberta T6G 2E1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-6950","authenticated-orcid":false,"given":"Marilaine","family":"Fournier","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0122-3746","authenticated-orcid":false,"given":"Troy A","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Alberta , Edmonton, Alberta T6G 2E1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-3437","authenticated-orcid":false,"given":"Judith N","family":"Mandl","sequence":"additional","affiliation":[{"name":"Department of Physiology and McGill Research Centre for Complex Traits, McGill University , Montreal, Quebec H3G 1Y6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-334X","authenticated-orcid":false,"given":"Heather J","family":"Melichar","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Center , Montreal, Quebec H1T 2M4,","place":["Canada"]},{"name":"Department of Medicine, University of Montreal , Montreal, Quebec H3T 1J4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025030614215650400_r1","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1016\/S0264-410X(01)00028-7","article-title":"Neonatal and early life vaccinology","volume":"19","author":"Siegrist","year":"2001","journal-title":"Vaccine"},{"key":"2025030614215650400_r2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri1394","article-title":"Neonatal adaptive immunity comes of age","volume":"4","author":"Adkins","year":"2004","journal-title":"Nat. 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