{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:01:54Z","timestamp":1792598514299,"version":"4.5.0"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":123,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Senior Investigator","award":["220295\/Z\/20\/Z"],"award-info":[{"award-number":["220295\/Z\/20\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The intracellular proteome of virtually every nucleated cell in the body is continuously presented at the cell surface via the human leukocyte antigen class I (HLA-I) antigen processing pathway. This pathway classically involves proteasomal degradation of intracellular proteins into short peptides that can be presented by HLA-I molecules for interrogation by T-cell receptors (TCRs) expressed on the surface of CD8+ T cells. During the initiation of a T-cell immune response, the TCR acts as the T cell\u2019s primary sensor, using flexible loops to mould around the surface of the pHLA-I molecule to identify foreign or dysregulated antigens. Recent findings demonstrate that pHLA-I molecules can also be highly flexible and dynamic, altering their shape according to minor polymorphisms between different HLA-I alleles, or interactions with different peptides. These flexible presentation modes have important biological consequences that can, for example, explain why some HLA-I alleles offer greater protection against HIV, or why some cancer vaccine approaches have been ineffective. This review explores how these recent findings redefine the rules for peptide presentation by HLA-I molecules and extend our understanding of the molecular mechanisms that govern TCR-mediated antigen discrimination.<\/jats:p>","DOI":"10.1093\/discim\/kyac001","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T20:12:58Z","timestamp":1651781578000},"source":"Crossref","is-referenced-by-count":15,"title":["Unconventional modes of peptide\u2013HLA-I presentation change the rules of TCR engagement"],"prefix":"10.1093","volume":"1","author":[{"given":"Jade R","family":"Hopkins","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine , Heath Park, Cardiff , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-2733","authenticated-orcid":false,"given":"Bruce J","family":"MacLachlan","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine , Heath Park, Cardiff , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6029-8668","authenticated-orcid":false,"given":"Stephen","family":"Harper","sequence":"additional","affiliation":[{"name":"Immunocore , Abingdon , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K","family":"Sewell","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine , Heath Park, Cardiff , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-9396","authenticated-orcid":false,"given":"David K","family":"Cole","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and 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IFA.","volume":"4","author":"Li\u00e9nard","year":"2004","journal-title":"Cancer Immun"},{"key":"2022081905171525000_CIT0095","doi-asserted-by":"crossref","first-page":"27281","DOI":"10.1074\/jbc.M109.022509","article-title":"Germ Line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.","volume":"284","author":"Cole","year":"2009","journal-title":"J Biol Chem"},{"key":"2022081905171525000_CIT0096","doi-asserted-by":"crossref","first-page":"4625","DOI":"10.4049\/jimmunol.1001480","article-title":"CD8 controls T cell cross-reactivity.","volume":"185","author":"Wooldridge","year":"2010","journal-title":"J Immunol"},{"key":"2022081905171525000_CIT0097","doi-asserted-by":"crossref","first-page":"23799","DOI":"10.1074\/jbc.M700976200","article-title":"Different T cell receptor affinity thresholds and CD8 coreceptor dependence govern cytotoxic T lymphocyte activation and tetramer binding 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