{"id":19761,"date":"2024-11-23T18:15:19","date_gmt":"2024-11-23T17:15:19","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/the-peptide-selectivity-model-interpreting-nk-cell-kir-hla-i-binding-interactions-and-their-associations-to-human-diseases-malcolm-j-w-sim\/"},"modified":"2024-11-23T18:15:19","modified_gmt":"2024-11-23T17:15:19","slug":"the-peptide-selectivity-model-interpreting-nk-cell-kir-hla-i-binding-interactions-and-their-associations-to-human-diseases-malcolm-j-w-sim","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/the-peptide-selectivity-model-interpreting-nk-cell-kir-hla-i-binding-interactions-and-their-associations-to-human-diseases-malcolm-j-w-sim\/","title":{"rendered":"The peptide selectivity model: Interpreting NK cell KIR-HLA-I binding interactions and their associations to human diseases. Malcolm J W Sim"},"content":{"rendered":"<div>\n<p>Trends Immunol. 2024 Nov 21:S1471-4906(24)00252-7. doi: 10.1016\/j.it.2024.10.006. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Combinations of the highly polymorphic KIR and HLA-I genes are associated with numerous human diseases. Interpreting these associations requires a molecular understanding of the multiple killer-cell immunoglobulin-like receptor (KIR)-human leukocyte antigen-1 (HLA-I) receptor-ligand interactions on natural killer (NK) cells and identifying the salient features that underlie disease risk. We hypothesize that a critical discriminating factor in KIR-HLA-I interactions is the selective detection of HLA-I-bound peptides by KIRs. We propose a &#8216;peptide selectivity model&#8217;, where high-avidity KIR-HLA-I interactions reflect low selectivity for peptides conferring consistent NK cell inhibition across different tissue immunopeptidomes. Conversely, lower-avidity interactions (including those with activating KIRs) are more dependent on HLA-I-bound peptide sequence, requiring an appreciation of how HLA-I immunopeptidomes influence KIR binding and regulate NK cell function. Relevant to understanding NK cell function and pathology, we interpret known KIR-HLA-I combinations and their associations with certain human diseases in the context of this &#8216;peptide selectivity model&#8217;.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39578117\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=100966032&amp;ff=20241123121518&amp;v=2.18.0.post9+e462414\">39578117<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.it.2024.10.006\">10.1016\/j.it.2024.10.006<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Trends Immunol. 2024 Nov 21:S1471-4906(24)00252-7. doi: 10.1016\/j.it.2024.10.006. Online ahead of print. ABSTRACT Combinations of the highly polymorphic KIR and HLA-I genes are associated with numerous human diseases. Interpreting these associations requires a molecular understanding of the multiple killer-cell immunoglobulin-like receptor (KIR)-human leukocyte antigen-1 (HLA-I) receptor-ligand interactions on natural killer (NK) cells and identifying the salient &#8230; <a title=\"The peptide selectivity model: Interpreting NK cell KIR-HLA-I binding interactions and their associations to human diseases. Malcolm J W Sim\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/the-peptide-selectivity-model-interpreting-nk-cell-kir-hla-i-binding-interactions-and-their-associations-to-human-diseases-malcolm-j-w-sim\/\" aria-label=\"Read more about The peptide selectivity model: Interpreting NK cell KIR-HLA-I binding interactions and their associations to human diseases. Malcolm J W Sim\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,68],"tags":[],"class_list":["post-19761","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-trends-in-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19761","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=19761"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19761\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=19761"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=19761"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=19761"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}