{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:00:31Z","timestamp":1790186431608,"version":"4.1.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Cytotoxic T lymphocytes form a critical component of SARS-CoV-2 immunity by recognizing viral peptides bound to HLA class I molecules. Here, we identified the spike-derived peptide NYNYLYRLF\n                    <jats:sub>448-456<\/jats:sub>\n                    (NF9) as the immunodominant HLA-A*24:02\u2013restricted epitope in both convalescent and vaccinated donors. Across cohorts, A24\/NF9-specific responses were dominated by public TCR motifs featuring TRAV12-1 paired with TRBJ2-7 and a conserved CDR3\u03b2 sequence (CASSXXXGYEQYF). Using a panel of 13 TCRs, we mapped recognition of single amino acid substitutions within NF9 and identified residue 5 (L452) as the principal determinant of escape. The L452R substitution, characteristic of the Delta variant, abolished recognition across all tested TCRs despite preserved HLA binding. Crystallography of a representative public TCR (P1-15) revealed that mutation at position-5 reoriented the peptide within HLA-A*24:02, flipping the adjacent Y453 side chain into the peptide-binding groove and eliminating the dominant TCR contact. This position-5\u2013driven conformational switch provided a structural mechanism for universal loss of NF9 recognition by HLA-A*24:02\u2013restricted T cells. Consistent with this, Delta-infected convalescents failed to mount de novo NF9-5R\u2013specific responses while retaining responses to the conserved A24\/QI9 spike epitope. Together, these findings defined the basis of A24\/NF9 recognition and showed how 1 mutation remodeled peptide presentation to abrogate TCR responses.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>A mutation in SARS-CoV-2 flips a viral fragment, hiding it from immune T-cells and allowing the virus to evade an important immune response.<\/jats:p>","DOI":"10.1172\/jci.insight.202235","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:00:22Z","timestamp":1773763222000},"source":"Crossref","is-referenced-by-count":1,"title":["Position-5\u2013driven reorientation of an immunodominant HLA-A*24:02 SARS-CoV-2 epitope drives universal T cell escape"],"prefix":"10.1172","volume":"11","author":[{"given":"Takeshi","family":"Nakama","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Wall","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-9108","authenticated-orcid":true,"given":"Garry","family":"Dolton","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Rong","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Hamana","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Aritsu","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toong Seng","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Goto","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanyu","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Kitamatsu","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Udaka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Kochi University, Kochi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, and"},{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Oshiumi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Nagasaki","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Clinical Research Institute, NHO, Kyushu Medical Center, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumi","family":"Minami","sequence":"additional","affiliation":[{"name":"Internal Medicine, Clinical Research Institute, NHO, Kyushu Medical Center, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Nakata","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto University Hospital, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-0369","authenticated-orcid":true,"given":"Pierre J.","family":"Rizkallah","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-4236","authenticated-orcid":true,"given":"Takamasa","family":"Ueno","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-3135","authenticated-orcid":true,"given":"Andrew K.","family":"Sewell","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."},{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Motozono","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.038"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108728"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202617"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.017"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf3698"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg5669"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06331-x"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature07746"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.07.002"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34033-x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg6461"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103353"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.06.006"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33068-4"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112827"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01351-7"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.008"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02017-08"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05538-8"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069660"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.12.008"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/srep33334"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-022-00239-1"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2342"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302667"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081127"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1029"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32989-4"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02885-6"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02143-23"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.05.015"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12482"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01184-4"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01162-22"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00575-3"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-005-0004-2"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30912-9"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5727"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107563"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109708"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nri1417"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12952-12960.2005"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.017"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110218"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-02051-0"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0149-5"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.707414"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-006-0185-3"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409427200"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/384134a0"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.12.009"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00296"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910009005"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.06.007"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911001314"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/202235\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:28:57Z","timestamp":1778786937000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/202235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":58,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5,8]]},"published-print":{"date-parts":[[2026,5,8]]}},"alternative-id":["10.1172\/jci.insight.202235"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.202235","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"article-number":"e202235"}}