ArticlePLoS biology2019
Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04426253 (Identification of Genetic Factors Determining Disease Course and Preparation of Pharmacogenetic Applications in the New Type of Coronavirus Infection, COVID-19), which is not on this map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Identification of Genetic Factors Determining Disease Course and Preparation of Pharmacogenetic Applications in the New Type of Coronavirus Infection, COVID-19
Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
- HLA-II peptide-binding diversity shapes humoral immune responses and susceptibility to infections.Nature communications · 2026Article
- Defining the molecular interaction between influenza hemagglutinin and MHC-II.bioRxiv : the preprint server for biology · 2026Article
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Adaptive radiation and structural tailoring of the VietnameseFrontiers in genetics · 2026Article
- Can the simple chicken MHC provide insight into the balance of autoimmunity and infectious disease?Immunogenetics · 2025Review
- Different HLA Alleles Frequencies and Their Association with Clinical Phenotypes of Acute Respiratory Infections in Children.Viruses · 2025Article
- Haplotype analysis reveals pleiotropic disease associations in the HLA region.American journal of human genetics · 2025Article
- Pathogen Adaptation of HLA Alleles and Its Correlation with Autoimmune Diseases in the Han Chinese.Genomics, proteomics & bioinformatics · 2025Article
- Early human migration determines the risk of being attacked by wolves: ethnic gene diversity on the development of systemic lupus erythematosus.Journal of rheumatic diseases · 2024Review
- Europeans and Americans of European origin show differences between their biological pathways related to the major histocompatibility complex.Scientific reports · 2024Article
- Haplotype Analysis Reveals Pleiotropic Disease Associations in the HLA Region.medRxiv : the preprint server for health sciences · 2024Article
- A journey to your self: The vague definition of immune self and its practical implications.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Evolution of T cells in the cancer-resistant naked mole-rat.Nature communications · 2024Article
- Article
- Host Transcriptional Regulatory Genes and Microbiome Networks Crosstalk through Immune Receptors Establishing Normal and Tumor Multiomics Metafirm of the Oral-Gut-Lung Axis.International journal of molecular sciences · 2023Review
- Pathogens are an important driving force for the rapid spread of symbionts in an insect host.Nature ecology & evolution · 2023Article
- High functional allelic diversity and copy number in both MHC classes in the common buzzard.BMC ecology and evolution · 2023Article
- The impact of HLA polymorphism on herpesvirus infection and disease.Immunogenetics · 2023Review
- Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA.Human molecular genetics · 2023Article
- Incidence of respiratory virus illness and hospitalizations in a Panama and El Salvador birth cohort, 2014-2018.Lancet regional health. Americas · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex (MHC), which shape the immune response against pathogens and tolerance to self-peptides. The corresponding genomic region is of particular interest, as it harbors more disease associations than any other region in the human genome, including associations with infectious diseases, autoimmune disorders, cancers, and neuropsychiatric diseases. Certain MHC molecules can bind to a much wider range of epitopes than others, but the functional implication of such an elevated epitope-binding repertoire has remained largely unclear. It has been suggested that by recognizing more peptide segments, such promiscuous MHC molecules promote immune response against a broader range of pathogens. If so, the geographical distribution of MHC promiscuity level should be shaped by pathogen diversity. Three lines of evidence support the hypothesis. First, we found that in pathogen-rich geographical regions, humans are more likely to carry highly promiscuous MHC class II DRB1 alleles. Second, the switch between specialist and generalist antigen presentation has occurred repeatedly and in a rapid manner during human evolution. Third, molecular positions that define promiscuity level of MHC class II molecules are especially diverse and are under positive selection in human populations. Taken together, our work indicates that pathogen load maintains generalist adaptive immune recognition, with implications for medical genetics and epidemiology.
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Registered trials
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.