ArticleNature genetics2022
HLA autoimmune risk alleles restrict the hypervariable region of T cell receptors.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome.Communications biology · 2025Pooled it
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects.Journal of cellular biochemistry · 2026Review
- Genetic architecture of cytokine autoantibodies and associated risk of common diseases.Nature communications · 2026Article
- A Comprehensive HLA-DR4 MHC Class II Tetramer Platform for the Detection and Functional Validation of Post-Translational Modification Neoantigens.International journal of molecular sciences · 2026Article
- Review
- Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy.MedComm · 2026Review
- Review
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood.Science advances · 2026Article
- Clonally expanded HSP-specific T cells contribute to glaucomatous neurodegeneration via the mTORC1 pathway.Journal of neuroinflammation · 2026Article
- T cell receptor clonotypes predict human leukocyte antigen allele carriage and antigen exposure history.Communications biology · 2026Article
- Autophagy in Rheumatoid Arthritis: Molecular Mechanisms, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.Inflammation · 2026Review
- Dissecting the Genetic Basis of Low Back Pain Independent of BMI Through Genomic Structural Equation Modeling.Journal of pain research · 2026Article
- Proanthocyanidins in immune-mediated inflammatory diseases: molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- Assessment of computational methods in predicting TCR-epitope binding recognition.Nature methods · 2026Article
- Genetic and environmental imprints on T cell receptor repertoires as predictors of graft-versus-host disease.bioRxiv : the preprint server for biology · 2025Article
- HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways.medRxiv : the preprint server for health sciences · 2025Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Polymorphisms in the human leukocyte antigen (HLA) genes strongly influence autoimmune disease risk. HLA risk alleles may influence thymic selection to increase the frequency of T cell receptors (TCRs) reactive to autoantigens (central hypothesis). However, research in human autoimmunity has provided little evidence supporting the central hypothesis. Here we investigated the influence of HLA alleles on TCR composition at the highly diverse complementarity determining region 3 (CDR3), which confers antigen recognition. We observed unexpectedly strong HLA-CDR3 associations. The strongest association was found at HLA-DRB1 amino acid position 13, the position that mediates genetic risk for multiple autoimmune diseases. We identified multiple CDR3 amino acid features enriched by HLA risk alleles. Moreover, the CDR3 features promoted by the HLA risk alleles are more enriched in candidate pathogenic TCRs than control TCRs (for example, citrullinated epitope-specific TCRs in patients with rheumatoid arthritis). Together, these results provide genetic evidence supporting the central hypothesis.
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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.