{"id":322979,"date":"2016-11-16T12:36:11","date_gmt":"2016-11-16T20:36:11","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/?post_type=msr-research-item&p=322979"},"modified":"2018-10-16T22:22:04","modified_gmt":"2018-10-17T05:22:04","slug":"influence-hla-c-expression-level-hiv-control","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/influence-hla-c-expression-level-hiv-control\/","title":{"rendered":"Influence of HLA-C Expression Level on HIV Control"},"content":{"rendered":"

HLA-C expression and HIV immune control<\/h1>\n

\"\"In collaboration with Mary Carrington’s<\/a> group, we showed in Science<\/a> that the quantity of HLA-C surface protein correlates with HIV disease progression, the probability than HLA-C epitopes will be targeted by the immune system, and the probability that HIV will escape within those epitopes. Mary further showed that HLA-C expression levels are linked to some auto-immune diseases. This is an important study that highlights the the role of HLA-C (which is generally ignored in the field) and de\"\"monstrates how our models of selection can be used to generate and test hypotheses. As always, this was a hugely collaborative effort, making key use of data from Philip Goulder, Zabrina Brumme and many others. The MSR Connections team wrote a blog post<\/a> providing a nice high-level description.<\/p>\n

Abstract<\/h2>\n

A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn\u2019s disease, suggesting a broader influence of HLA expression levels in human disease.<\/p>\n","protected":false},"excerpt":{"rendered":"

HLA-C expression and HIV immune control In collaboration with Mary Carrington’s group, we showed in Science that the quantity of HLA-C surface protein correlates with HIV disease progression, the probability than HLA-C epitopes will be targeted by the immune system, and the probability that HIV will escape within those epitopes. Mary further showed that HLA-C […]<\/p>\n","protected":false},"featured_media":446343,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","footnotes":""},"msr-content-type":[3],"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-product-type":[],"msr-focus-area":[],"msr-platform":[],"msr-download-source":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[],"msr-conference":[],"msr-journal":[],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-322979","msr-research-item","type-msr-research-item","status-publish","has-post-thumbnail","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"","msr_edition":"Science","msr_affiliation":"","msr_published_date":"2013-04-05","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"87-91","msr_chapter":"","msr_isbn":"","msr_journal":"Science","msr_volume":"340","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"6128","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":1,"msr_main_download":"","msr_publicationurl":"http:\/\/science.sciencemag.org\/content\/340\/6128\/87","msr_doi":"10.1126\/science.1232685","msr_publication_uploader":[{"type":"url","title":"http:\/\/science.sciencemag.org\/content\/340\/6128\/87","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1126\/science.1232685","viewUrl":false,"id":false,"label_id":0}],"msr_related_uploader":"","msr_attachments":[{"id":0,"url":"http:\/\/science.sciencemag.org\/content\/340\/6128\/87"}],"msr-author-ordering":[{"type":"text","value":"Richard Apps","user_id":0,"rest_url":false},{"type":"text","value":"Ying Qi","user_id":0,"rest_url":false},{"type":"user_nicename","value":"carlson","user_id":31333,"rest_url":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=carlson"},{"type":"text","value":"Haoyan Chen","user_id":0,"rest_url":false},{"type":"text","value":"Xiaojiang Gao","user_id":0,"rest_url":false},{"type":"text","value":"Rasmi Thomas","user_id":0,"rest_url":false},{"type":"text","value":"Yuko Yuki","user_id":0,"rest_url":false},{"type":"text","value":"Greg Q. 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