ArticleProceedings of the National Academy of Sciences of the United States of America2019
HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Detailed stratified GWAS analysis for severe COVID-19 in four European populations.Human molecular genetics · 2022Pooled it
- Co-regulation of HIV control and cytomegalovirus pp65-specific IL-1β and TNF-α responses by genetic variants in the MHC region.PLoS pathogens · 2026Article
- Ancient DNA study provides clues to leprosy susceptibility in medieval Europe.Genome biology · 2026Article
- Immunogenetic Predisposition to SARS-CoV-2 Infection.Biology · 2022Article
- Evolutionary pressures rendered by animal husbandry practices for avian influenza viruses to adapt to humans.iScience · 2022Review
- Challenging Ancient DNA Results About Putative HLA Protection or Susceptibility to Yersinia pestis.Molecular biology and evolution · 2022Article
- Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond.Frontiers in immunology · 2022Review
- Article
- Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity.The Journal of infectious diseases · 2021Article
- HIV-1 and human genetic variation.Nature reviews. Genetics · 2021Review
- Unique Pathogen Peptidomes Facilitate Pathogen-Specific Selection and Specialization of MHC Alleles.Molecular biology and evolution · 2021Article
- Chickens as a simple system for scientific discovery: The example of the MHC.Molecular immunology · 2021Article
- Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals.Scientific reports · 2021Article
- Minding the gap in HIV host genetics: opportunities and challenges.Human genetics · 2020Review
- HLA Heterozygote Advantage against HIV-1 Is Driven by Quantitative and Qualitative Differences in HLA Allele-Specific Peptide Presentation.Molecular biology and evolution · 2020Article
- Does Antigen Glycosylation Impact the HIV-Specific T Cell Immunity?Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Genetic variation in the peptide-binding groove of the highly polymorphic HLA class I molecules has repeatedly been associated with HIV-1 control and progression to AIDS, accounting for up to 12% of the variation in HIV-1 set point viral load (spVL). This suggests a key role in disease control for HLA presentation of HIV-1 epitopes to cytotoxic T cells. However, a comprehensive understanding of the relevant HLA-bound HIV epitopes is still elusive. Here we describe a peptidome-wide association study (PepWAS) approach that integrates HLA genotypes and spVL data from 6,311 HIV-infected patients to interrogate the entire HIV-1 proteome (3,252 unique peptides) for disease-relevant peptides. This PepWAS approach predicts a core set of epitopes associated with spVL, including known epitopes but also several previously uncharacterized disease-relevant peptides. More important, each patient presents only a small subset of these predicted core epitopes through their individual HLA-A and HLA-B variants. Eventually, the individual differences in these patient-specific epitope repertoires account for the variation in spVL that was previously associated with HLA genetic variation. PepWAS thus enables a comprehensive functional interpretation of the robust but little-understood association between HLA and HIV-1 control, prioritizing a short list of disease-associated epitopes for the development of targeted therapy.
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