{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:11:48Z","timestamp":1773724308716,"version":"3.50.1"},"reference-count":40,"publisher":"The Royal Society","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"crossref","award":["091664\/B\/10\/Z"],"award-info":[{"award-number":["091664\/B\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010438","name":"The Francis Crick Institute","doi-asserted-by":"crossref","award":["FC001076"],"award-info":[{"award-number":["FC001076"]}],"id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI033456"],"award-info":[{"award-number":["R01 AI033456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCR\u03b1 and \u03b2 genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity\u2014hence reactivity to self\u2014and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2<jats:sup>b<\/jats:sup>haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L<jats:sup>d<\/jats:sup>-restricted epitope, derived from the Rop7 protein of<jats:italic>Toxoplasma gondii<\/jats:italic>. We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels. First, we demonstrate the common occurrence of secondary rearrangements in endogenously rearranged loci. Furthermore, we characterized and compared the response of Rop7-specific CD8 T-cell clones upon<jats:italic>Toxoplasma gondii<\/jats:italic>infection as well as effector function and TCR signalling upon antigenic stimulation<jats:italic>in vitro<\/jats:italic>. Antigen-independent TCR cross-linking<jats:italic>in vitro<\/jats:italic>uncovered profound intrinsic differences in the effector functions between T-cell clones. Finally, by assessing the degree of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we show that lower self-reactivity correlates with lower effector capacity, whereas higher self-reactivity is associated with enhanced effector function as well as cell cycle entry under physiological conditions. Altogether, our data show that potential effector functions and basal proliferation of CD8 T cells are set by self-reactivity thresholds.<\/jats:p>","DOI":"10.1098\/rsob.160293","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T10:10:21Z","timestamp":1479895821000},"page":"160293","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions"],"prefix":"10.1098","volume":"6","author":[{"given":"Lee Kim","family":"Swee","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, National University of Singapore, Singapore"},{"name":"Department of Biological Sciences, Immunology Programme, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sanecka","sequence":"additional","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagisa","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshil","family":"Patel","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gijsbert","family":"Grotenbreg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, National University of Singapore, Singapore"},{"name":"Department of Biological Sciences, Immunology Programme, National University of Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-3442","authenticated-orcid":false,"given":"Eva-Maria","family":"Frickel","sequence":"additional","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidde L.","family":"Ploegh","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2016,11]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.523"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(89)90307-1"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/46218"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067833"},{"key":"e_1_3_7_7_2","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.4049\/jimmunol.160.8.3705","article-title":"MHC class I is required for peripheral accumulation of CD8+ thymic emigrants","volume":"160","author":"Nesi\u0107 D","year":"1998","journal-title":"J. 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