ArticleThe Journal of clinical investigation2015
Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.Nature genetics · 2016Pooled it
- A Single Amino Acid Polymorphism Within the α2 Domain of HLA-DQα Regulates the Assembly and Expression of HLA DQ Alleles and the Potential Clinical Impact.Transplantation · 2026Article
- Association Between Donor HLA-DQ Heterodimers Group and Graft Loss in Kidney Transplant Recipients.Transplantation direct · 2026Article
- Structural Modulation and Binding of HLA-DQ8 by Cysteine-to-Serine Mutated Insulin Peptide: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- The Hunt for HLA-DQ Allogeneic Eplets Is Not Over: Four New Ones, Including a Cross-Chain Eplet.HLA · 2025Article
- Genetic aspects of pediatric nephrotic syndrome and anti-nephrin antibodies.Clinical and experimental nephrology · 2025Review
- HLA class II-restricted T cell epitopes in public neoantigens of ESR1 and PIK3CA in breast cancer.BMC cancer · 2025Article
- Crucial Parameters for Immunopeptidome Characterization: A Systematic Evaluation.International journal of molecular sciences · 2024Article
- HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.Brain : a journal of neurology · 2024Article
- Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.Frontiers in immunology · 2024Review
- Non-mutational neoantigens in disease.Nature immunology · 2024Review
- Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing.International journal of molecular sciences · 2023Article
- Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility.American journal of human genetics · 2023Article
- Narcolepsy type I-associated DNA methylation and gene expression changes in the human leukocyte antigen region.Scientific reports · 2023Article
- Genome-wide association study of 7661 Chinese Han individuals and fine-mapping major histocompatibility complex identifies HLA-DRB1 as associated with IgA vasculitis.Journal of clinical laboratory analysis · 2022Article
- A previously unappreciated polymorphism in the beta chain of I-AMolecular immunology · 2022Article
- High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD).Scientific reports · 2022Article
- New insights on the role of human leukocyte antigen complex in primary biliary cholangitis.Frontiers in immunology · 2022Review
- HLA imputation and its application to genetic and molecular fine-mapping of the MHC region in autoimmune diseases.Seminars in immunopathology · 2022Review
- Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope.Nature communications · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polymorphisms within HLA gene loci are strongly associated with susceptibility to autoimmune disorders; however, it is not clear how genetic variations in these loci confer a disease risk. Here, we devised a cell-surface MHC expression assay to detect allelic differences in the intrinsic stability of HLA-DQ proteins. We found extreme variation in cell-surface MHC density among HLA-DQ alleles, indicating a dynamic allelic hierarchy in the intrinsic stability of HLA-DQ proteins. Using the case-control data for type 1 diabetes (T1D) for the Swedish and Japanese populations, we determined that T1D risk-associated HLA-DQ haplotypes, which also increase risk for autoimmune endocrinopathies and other autoimmune disorders, encode unstable proteins, whereas the T1D-protective haplotypes encode the most stable HLA-DQ proteins. Among the amino acid variants of HLA-DQ, alterations in 47α, the residue that is located on the outside of the peptide-binding groove and acts as a key stability regulator, showed strong association with T1D. Evolutionary analysis suggested that 47α variants have been the target of positive diversifying selection. Our study demonstrates a steep allelic hierarchy in the intrinsic stability of HLA-DQ that is associated with T1D risk and protection, suggesting that HLA instability mediates the development of autoimmune disorders.
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