{"id":168812,"date":"2015-10-20T00:00:00","date_gmt":"2015-10-20T00:00:00","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/msr-research-item\/selector-function-of-mhc-i-molecules-is-determined-by-protein-plasticity\/"},"modified":"2018-10-16T21:29:33","modified_gmt":"2018-10-17T04:29:33","slug":"selector-function-of-mhc-i-molecules-is-determined-by-protein-plasticity","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/selector-function-of-mhc-i-molecules-is-determined-by-protein-plasticity\/","title":{"rendered":"Selector function of MHC I molecules is determined by protein plasticity"},"content":{"rendered":"<div class=\"asset-content\">\n<p>The selection of peptides for presentation at the surface of most nucleated cells by major histocompatibility complex class I molecules (MHC I) is crucial to the immune response in vertebrates. However, the mechanisms of the rapid selection of high affinity peptides by MHC I from amongst thousands of mostly low affinity peptides are not well understood. We developed computational systems models encoding distinct mechanistic hypotheses for two molecules, HLA-B*44:02 (B*4402) and HLA-B*44:05 (B*4405), which differ by a single residue yet lie at opposite ends of the spectrum in their intrinsic ability to select high affinity peptides. We used <em>in vivo<\/em> biochemical data to infer that a conformational intermediate of MHC I is significant for peptide selection. We used molecular dynamics simulations to show that peptide selector function correlates with protein plasticity, and confirmed this experimentally by altering the plasticity of MHC I with a single point mutation, which altered <em>in vivo<\/em> selector function in a predictable way. Finally, we investigated the mechanisms by which the co-factor tapasin influences MHC I plasticity. We propose that tapasin modulates MHC I plasticity by dynamically coupling the peptide binding region and \u03b1<sub>3<\/sub> domain of MHC I allosterically, resulting in enhanced peptide selector function.<\/p>\n<\/div>\n<p><!-- .asset-content --><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The selection of peptides for presentation at the surface of most nucleated cells by major histocompatibility complex class I molecules (MHC I) is crucial to the immune response in vertebrates. However, the mechanisms of the rapid selection of high affinity peptides by MHC I from amongst thousands of mostly low affinity peptides are not well [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"Nature Publishing Group","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"Scientific Reports","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"Scientific Reports","msr_number":"","msr_organization":"","msr_pages_string":"14928","msr_page_range_start":"14928","msr_page_range_end":"","msr_series":"","msr_volume":"5","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1038\/srep14928","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"Alistair Bailey, Rachel Carter, J\u00f6rn M. 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Building a platform for programming biology The ability to program biology could enable fundamental breakthroughs across a broad range of industries, including medicine, agriculture, food, construction, textiles, materials and chemicals. It could also help lay the foundation for a future bioeconomy based on sustainable technology. Despite&hellip;","_links":{"self":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-project\/544545"}]}},{"ID":292901,"post_title":"Modelling Immune System Processes","post_name":"modelling-immune-system-processes","post_type":"msr-project","post_date":"2016-09-14 12:28:15","post_modified":"2020-07-08 06:47:34","post_status":"publish","permalink":"https:\/\/www.microsoft.com\/en-us\/research\/project\/modelling-immune-system-processes\/","post_excerpt":"Immunodominance lies at the heart of the immune system's ability to distinguish self from non-self. Understanding and possibly controlling the mechanisms that govern immunodominance will have profound consequences for the fight against several classes of diseases, including viral infections and cancer. We have been attempting to understand the computation performed by the immune system that gives rise to immunodominance, using techniques from computer science, applied mathematics and Bayesian statistics. &nbsp; &nbsp;","_links":{"self":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-project\/292901"}]}}]},"_links":{"self":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/168812","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item"}],"about":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-research-item"}],"version-history":[{"count":1,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/168812\/revisions"}],"predecessor-version":[{"id":435390,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/168812\/revisions\/435390"}],"wp:attachment":[{"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/media?parent=168812"}],"wp:term":[{"taxonomy":"msr-research-highlight","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-research-highlight?post=168812"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=168812"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=168812"},{"taxonomy":"msr-publisher","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-publisher?post=168812"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=168812"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=168812"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=168812"},{"taxonomy":"msr-field-of-study","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-field-of-study?post=168812"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=168812"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=168812"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=168812"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=168812"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}