Discovery immunologyPub Date : 2022-05-10eCollection Date: 2022-01-01DOI: 10.1093/discim/kyac002
Sophie Curio, Sarah C Edwards, Toshiyasu Suzuki, Jenny McGovern, Chiara Triulzi, Nagisa Yoshida, Gustav Jonsson, Teresa Glauner, Damiano Rami, Robert Wiesheu, Anna Kilbey, Rachel Violet Purcell, Seth B Coffelt, Nadia Guerra
{"title":"NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression.","authors":"Sophie Curio, Sarah C Edwards, Toshiyasu Suzuki, Jenny McGovern, Chiara Triulzi, Nagisa Yoshida, Gustav Jonsson, Teresa Glauner, Damiano Rami, Robert Wiesheu, Anna Kilbey, Rachel Violet Purcell, Seth B Coffelt, Nadia Guerra","doi":"10.1093/discim/kyac002","DOIUrl":"10.1093/discim/kyac002","url":null,"abstract":"<p><p>γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance, homeostasis, and cancer. γδT cells recognize stressed cells or cancer cells through the NKG2D receptor to kill these cells and maintain normality. Contrary to the well-established anti-tumor function of these NKG2D-expressing γδT cells, we show here that, in mice, NKG2D regulates a population of pro-tumor γδT cells capable of producing IL-17A. Germline deletion of <i>Klrk1</i>, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduced the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increased the frequency of γδT cells. Together, these data support the hypothesis that, in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"1 1","pages":"kyac002"},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/df/kyac002.PMC9580227.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729686","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}
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}