ArticleMolecular biology and evolution2018
Divergent Allele Advantage at Human MHC Genes: Signatures of Past and Ongoing Selection.
Article in Molecular biology and evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
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- Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial.Nature medicine · 2023Trial
- High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab.Molecular cancer research : MCR · 2021Trial
- Towards quantifying immune diversity through HLA genomics.Nature reviews. Genetics · 2026Article
- A multicenter kidney transplantation study identifies hierarchy and directionality of HLA-DQ alloimmune responses.Nature communications · 2026Article
- Immunological Determinants of Oncogenic Virus-Driven Cancers in Africa: Mechanisms, Co-Infections and Public Health Challenges.Pathogens (Basel, Switzerland) · 2026Review
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- Signatures of pathogen-driven selection and Austronesian gene flow of Papua New Guinea HLA alleles.American journal of human genetics · 2026Article
- Immunological features of acquired pure red cell aplasia: Specific human leucocyte antigen alleles, signal transducer and activator of transcription 3 mutations and a unique T-cell receptor beta motif.British journal of haematology · 2026Article
- T-cell repertoire response in individuals with post-acute sequelae of COVID-19.bioRxiv : the preprint server for biology · 2026Article
- Higher HLA-DRB1 Evolutionary Divergence Is Associated with Reduced Relapse and Improved Survival after Matched Unrelated Hematopoietic Cell Transplantation.Transplantation and cellular therapy · 2026Article
- HLA-DQB1*03:01 and risk of HBV-related HCC.Hepatology (Baltimore, Md.) · 2026Article
- Genetic and environmental imprints on T cell receptor repertoires as predictors of graft-versus-host disease.bioRxiv : the preprint server for biology · 2025Article
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- No evidence for disassortative mating based on HLA in a small-scale, endogamous population.bioRxiv : the preprint server for biology · 2025Article
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- Inbreeding does not reduce major histocompatibility complex diversity in the banded mongoose.BMC ecology and evolution · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly polymorphic genes of the major histocompatibility complex (MHC) play a key role in adaptive immunity. Divergent allele advantage, a mechanism of balancing selection, is proposed to contribute to their exceptional polymorphism. It assumes that MHC genotypes with more divergent alleles allow for broader antigen-presentation to immune effector cells, by that increasing immunocompetence. However, the direct correlation between pairwise sequence divergence and the corresponding repertoire of bound peptides has not been studied systematically across different MHC genes. Here, we investigated this relationship for five key classical human MHC genes (human leukocyte antigen; HLA-A, -B, -C, -DRB1, and -DQB1), using allele-specific computational binding prediction to 118,097 peptides derived from a broad range of human pathogens. For all five human MHC genes, the genetic distance between two alleles of a heterozygous genotype was positively correlated with the total number of peptides bound by these two alleles. In accordance with the major antigen-presentation pathway of MHC class I molecules, HLA-B and HLA-C alleles showed particularly strong correlations for peptides derived from intracellular pathogens. Intriguingly, this bias coincides with distinct protein compositions between intra- and extracellular pathogens, possibly suggesting adaptation of MHC I molecules to present specifically intracellular peptides. Eventually, we observed significant positive correlations between an allele's average divergence and its population frequency. Overall, our results support the divergent allele advantage as a meaningful quantitative mechanism through which pathogen-mediated selection leads to the evolution of MHC diversity.
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