{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:16:02Z","timestamp":1790543762874,"version":"4.1.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Collaboration for the Genomics of HIV"},{"DOI":"10.13039\/100012728","name":"Frederick National Laboratory for Cancer Research","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program of the NIH"},{"DOI":"10.13039\/100012728","name":"Frederick National Lab","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Cancer Research"},{"name":"Emmy Noether Programme of the Deutsche Forschungsgemeinschaft","award":["LE 2593\/3-1 to T.L.L."],"award-info":[{"award-number":["LE 2593\/3-1 to T.L.L."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogen-mediated balancing selection is regarded as a key driver of host immunogenetic diversity. A hallmark for balancing selection in humans is the heterozygote advantage at genes of the human leukocyte antigen (HLA), resulting in improved HIV-1 control. However, the actual mechanism of the observed heterozygote advantage is still elusive. HLA heterozygotes may present a broader array of antigenic viral peptides to immune cells, possibly resulting in a more efficient cytotoxic T-cell response. Alternatively, heterozygosity may simply increase the chance to carry the most protective HLA alleles, as individual HLA alleles are known to differ substantially in their association with HIV-1 control. Here, we used data from 6,311 HIV-1-infected individuals to explore the relative contribution of quantitative and qualitative aspects of peptide presentation in HLA heterozygote advantage against HIV. Screening the entire HIV-1 proteome, we observed that heterozygous individuals exhibited a broader array of HIV-1 peptides presented by their HLA class I alleles. In addition, viral load was negatively correlated with the breadth of the HIV-1 peptide repertoire bound by an individual\u2019s HLA variants, particularly at HLA-B. This suggests that heterozygote advantage at HLA-B is at least in part mediated by quantitative peptide presentation. We also observed higher HIV-1 sequence diversity among HLA-B heterozygous individuals, suggesting stronger evolutionary pressure from HLA heterozygosity. However, HLA heterozygotes were also more likely to carry certain HLA alleles, including the highly protective HLA-B*57:01 variant, indicating that HLA heterozygote advantage ultimately results from a combination of quantitative and qualitative effects in antigen presentation.<\/jats:p>","DOI":"10.1093\/molbev\/msz249","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T19:09:23Z","timestamp":1571944163000},"page":"639-650","source":"Crossref","is-referenced-by-count":84,"title":["HLA Heterozygote Advantage against HIV-1 Is Driven by Quantitative and Qualitative Differences in HLA Allele-Specific Peptide Presentation"],"prefix":"10.1093","volume":"37","author":[{"given":"Jatin","family":"Arora","sequence":"first","affiliation":[{"name":"Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Pl\u00f6n, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Pierini","sequence":"first","affiliation":[{"name":"Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Pl\u00f6n, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"McLaren","sequence":"first","affiliation":[{"name":"JC Wilt Infectious Diseases Research Center, National HIV and Retrovirology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada"},{"name":"Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Carrington","sequence":"first","affiliation":[{"name":"Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD"},{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Fellay","sequence":"first","affiliation":[{"name":"Global Health Institute, School of Life Sciences, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, Lausanne, Switzerland"},{"name":"Swiss Institute of Bioinformatics, Lausanne, Switzerland"},{"name":"Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias L","family":"Lenz","sequence":"first","affiliation":[{"name":"Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Pl\u00f6n, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"issue":"6","key":"2020022407594708400_msz249-B1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/hmg\/ddg066","article-title":"Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC","volume":"12","author":"Ahmad","year":"2003","journal-title":"Hum Mol Genet"},{"key":"2020022407594708400_msz249-B2","doi-asserted-by":"crossref","first-page":"baw093","DOI":"10.1093\/database\/baw093","article-title":"The Ensembl gene annotation system","volume":"2016","author":"Aken","year":"2016","journal-title":"Database"},{"issue":"2","key":"2020022407594708400_msz249-B3","doi-asserted-by":"crossref","first-page":"179.","DOI":"10.1615\/CritRevImmunol.v17.i2.40","article-title":"The nature of selection on the major histocompatibility 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