{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T02:48:36Z","timestamp":1774234116820,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S024220\/1"],"award-info":[{"award-number":["MR\/S024220\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The CD8 co\u2010receptor exists as both an \u03b1\u03b1 homodimer, expressed on subsets of specialized lymphoid cells, and as an \u03b1\u03b2 heterodimer, which is the canonical co\u2010receptor on cytotoxic T\u2010cells, tuning TCR thymic selection and antigen\u2010reactivity in the periphery. However, the biophysical parameters governing human CD8\u03b1\u03b2 interactions with classical MHC class I (MHCI) and unconventional MHC\u2010like molecules have not been determined. Using hetero\u2010dimerized Fc\u2010fusions to generate soluble human CD8\u03b1\u03b2, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8\u03b1\u03b1. We observed that both forms of CD8 bound to certain alleles with stronger affinity than others and found that the affinity of thymically selected TCRs was inversely associated with the affinity of the CD8 co\u2010receptor for the different alleles. We further demonstrated the binding of CD8\u03b1\u03b1 and CD8\u03b1\u03b2 to the unconventional MHC\u2010like molecule, MHCI\u2010related protein 1, with a similar affinity as for classical MHCI, but no interaction was observed for the other unconventional MHC\u2010like molecules, CD1a, b, c, or d. In summary, this is the first characterization of human CD8\u03b1\u03b2 binding to MHCI and MHC\u2010like molecules that revealed an intriguing relationship between CD8 binding affinity for different MHCI alleles and the selection of TCRs in the thymus.<\/jats:p>","DOI":"10.1002\/eji.202451230","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T03:04:54Z","timestamp":1734663894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Human CD8\u03b1\u03b2 Interaction With Classical and Unconventional MHC Molecules"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8242-7671","authenticated-orcid":false,"given":"Ben","family":"de Wet","sequence":"first","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Alan","family":"Simmons","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Suckling","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Szoke\u2010Kovacs","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah","family":"Mansour","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine University of Southampton  Southampton UK"},{"name":"Versant Ventures\/Ridgeline Discovery  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Lepore","sequence":"additional","affiliation":[{"name":"Institute for Life Sciences University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David K.","family":"Cole","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra L.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milos","family":"Aleksic","sequence":"additional","affiliation":[{"name":"Immunocore Limited  Abingdon Oxon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500555200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90090-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01365"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2012.03625.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636243"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902398"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700976200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.042"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3889"},{"key":"e_1_2_8_12_1","first-page":"219","article-title":"CD8 coreceptor Engagement of MR1 Enhances Antigen Responsiveness by human MAIT and Other MR1\u2010reactive T Cells","author":"Souter M. 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