{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:33:40Z","timestamp":1788431620349,"version":"build-2803163510"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6680","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2024,1,19]]},"abstract":"<jats:p>\n            Heterozygosity of\n            <jats:italic>Human leukocyte antigen<\/jats:italic>\n            (\n            <jats:italic>HLA<\/jats:italic>\n            ) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles. Greater functional divergence for pairs of HLA-A and\/or HLA-B allotypes was associated with slower AIDS progression and independently with enhanced viral load control. The metric predicts immune breadth at the peptide level rather than gene level and redefines\n            <jats:italic>HLA<\/jats:italic>\n            heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where\n            <jats:italic>HLA<\/jats:italic>\n            heterozygote advantage occurs.\n          <\/jats:p>","DOI":"10.1126\/science.adk0777","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T18:59:12Z","timestamp":1705604352000},"page":"319-325","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Impact of HLA class I functional divergence on HIV control"],"prefix":"10.1126","volume":"383","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1737-8021","authenticated-orcid":true,"given":"Mathias","family":"Viard","sequence":"first","affiliation":[{"name":"Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 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