ArticleJournal of immunology (Baltimore, Md. : 1950)2011
An insertion mutant in DQA1*0501 restores susceptibility to HLA-DM: implications for disease associations.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Peripheral blood gene expression stratifies rate of progression to type 1 diabetes in autoantibody-positive children in the TEDDY study.Frontiers in immunology · 2025Article
- The MHC Class II Antigen-Processing and Presentation Pathway Is Dysregulated in Type 1 Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange.Nature chemical biology · 2023Article
- Protective HLA alleles against severe COVID-19: HLA-A*68 as an ancestral protection allele in Tapachula-Chiapas, Mexico.Clinical immunology (Orlando, Fla.) · 2022Article
- Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.Molecular & cellular proteomics : MCP · 2022Article
- Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease.Gastroenterology · 2020Article
- HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide-binding cleft.The Journal of biological chemistry · 2020Article
- Distinct editing functions of natural HLA-DM allotypes impact antigen presentation and CD4Cellular & molecular immunology · 2020Article
- Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Class II MHC antigen processing in immune tolerance and inflammation.Immunogenetics · 2019Review
- HLA-DO Modulates the Diversity of the MHC-II Self-peptidome.Molecular & cellular proteomics : MCP · 2019Article
- A TCRα framework-centered codon shapes a biased T cell repertoire through direct MHC and CDR3β interactions.JCI insight · 2017Article
- Unraveling the structural basis for the unusually rich association of human leukocyte antigen DQ2.5 with class-II-associated invariant chain peptides.The Journal of biological chemistry · 2017Article
- The Other Function: Class II-Restricted Antigen Presentation by B Cells.Frontiers in immunology · 2017Review
- MHC class II complexes sample intermediate states along the peptide exchange pathway.Nature communications · 2016Article
- Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.Open biology · 2016Review
- Type 1 diabetes associated HLA-DQ2 and DQ8 molecules are relatively resistant to HLA-DM mediated release of invariant chain-derived CLIP peptides.European journal of immunology · 2016Article
- pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity.Scientific reports · 2015Article
- Endogenous antigen processing drives the primary CD4+ T cell response to influenza.Nature medicine · 2015Article
- Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA.The Journal of clinical investigation · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
HLA-DM (DM) catalyzes CLIP release, stabilizes MHC class II molecules, and edits the peptide repertoire presented by class II. Impaired DM function may have profound effects on Ag presentation events in the thymus and periphery that are critical for maintenance of self-tolerance. The associations of the HLA-DQ2 (DQ2) allele with celiac disease and type 1 diabetes mellitus have been appreciated for a long time. The explanation for these associations, however, remains unknown. We previously found that DQ2 is a poor substrate for DM. In this study, to further characterize DQ2-DM interaction, we introduced point mutations into DQ2 on the proposed DQ2-DM interface to restore the sensitivity of DQ2 to DM. The effects of mutations were investigated by measuring the peptide dissociation and exchange rate in vitro, CLIP and DQ2 expression on the cell surface, and the presentation of α-II-gliadin epitope (residues 62-70) to murine, DQ2-restricted T cell hybridomas. We found that the three α-chain mutations (α+53G, α+53R, or αY22F) decreased the intrinsic stability of peptide-class II complex. More interestingly, the α+53G mutant restored DQ2 sensitivity to DM, likely due to improved interaction with DM. Our data also suggest that α-II-gliadin 62-70 is a DM-suppressed epitope. The DQ2 resistance to DM changes the fate of this peptide from a cryptic to an immunodominant epitope. Our findings elucidate the structural basis for reduced DQ2-DM interaction and have implications for mechanisms underlying disease associations of DQ2.
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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.