ArticleMolecular biology and evolution2020
HLA Heterozygote Advantage against HIV-1 Is Driven by Quantitative and Qualitative Differences in HLA Allele-Specific Peptide Presentation.
Article in Molecular biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 91 citations in OpenAlex.
- A multicenter kidney transplantation study identifies hierarchy and directionality of HLA-DQ alloimmune responses.Nature communications · 2026Article
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- HLA-DQB1*03:01 and risk of HBV-related HCC.Hepatology (Baltimore, Md.) · 2026Article
- Impact ofFrontiers in cellular and infection microbiology · 2026Article
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- Twenty years of tuberculosis-driven selection shaped the evolution of the meerkat major histocompatibility complex.Nature ecology & evolution · 2025Article
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- Donor HLA-DQ genetic and functional divergence affect the control of BK polyoma virus infection after kidney transplantation.Science advances · 2025Article
- Perspective: host factors variants and the underlying causes of long COVID.Frontiers in medicine · 2025Article
- HLA Class I (A and B) Allele Polymorphism in a Moroccan Population Infected with Hepatitis C Virus.Current issues in molecular biology · 2024Article
- HLA Genetic Diversity and Chronic Hepatitis B Virus Infection: Effect of Heterozygosity Advantage.Medical sciences (Basel, Switzerland) · 2024Article
- An immunogenetic basis for lung cancer risk.Science (New York, N.Y.) · 2024Article
- Limited associations between MHC diversity and reproductive success in a bird species with biparental care.Ecology and evolution · 2024Article
- Impact of HLA class I functional divergence on HIV control.Science (New York, N.Y.) · 2024Article
- Homozygosity in any HLA locus is a risk factor for specific antibody production: the taboo concept 2.0.Frontiers in immunology · 2024Article
- HLA Genes: A Hallmark of Functional Genetic Variation and Complex Evolution.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy.Nature reviews. Clinical oncology · 2023Review
- Tutorial: a statistical genetics guide to identifying HLA alleles driving complex disease.Nature protocols · 2023Review
- Understanding the evolution of immune genes in jawed vertebrates.Journal of evolutionary biology · 2023Review
- Solving the puzzle of what makes immunotherapies work.Trends in cancer · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
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's 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.