Discovery immunologyPub Date : 2022-05-04eCollection Date: 2022-01-01DOI: 10.1093/discim/kyac001
Jade R Hopkins, Bruce J MacLachlan, Stephen Harper, Andrew K Sewell, David K Cole
{"title":"Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.","authors":"Jade R Hopkins, Bruce J MacLachlan, Stephen Harper, Andrew K Sewell, David K Cole","doi":"10.1093/discim/kyac001","DOIUrl":"10.1093/discim/kyac001","url":null,"abstract":"<p><p>The intracellular proteome of virtually every nucleated cell in the body is continuously presented at the cell surface <i>via</i> 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<sup>+</sup> T cells. During the initiation of a T-cell immune response, the TCR acts as the T cell's 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.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac001"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42028673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery Immunology, a new Open Access journal from the British Society for Immunology","authors":"S. Milling","doi":"10.1093/discim/kyab002","DOIUrl":"https://doi.org/10.1093/discim/kyab002","url":null,"abstract":"","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48828553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}