ArticleProceedings of the National Academy of Sciences of the United States of America1995
Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis.The British journal of dermatology · 2012Pooled it
- Immunoregulatory effects of TPM203 peptide-nanoparticle therapy in pemphigus vulgaris.The British journal of dermatology · 2026Article
- JAK-STAT pathway, type I/II cytokines, and new potential therapeutic strategy for autoimmune bullous diseases: update on pemphigus vulgaris and bullous pemphigoid.Frontiers in immunology · 2025Review
- Cytokine profiling reveals HLA-linked Th2 and Th17 driven immune activation in pemphigus vulgaris patients and genetically susceptible healthy controls.Frontiers in immunology · 2024Article
- Healthy individuals genetically at-risk for the development of Pemphigus vulgaris or Alopecia areata share disease-like cytokine dysregulation.Frontiers in immunology · 2024Article
- T cell autoimmunity and immune regulation to desmoglein 3, a pemphigus autoantigen.The Journal of dermatology · 2023Review
- Understanding CD4Frontiers in immunology · 2023Review
- Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways.The Journal of investigative dermatology · 2022Review
- Patient genetics shape the autoimmune response in the blistering skin disease pemphigus vulgaris.Frontiers in immunology · 2022Article
- Detection of rare autoreactive T cell subsets in patients with pemphigus vulgaris.Frontiers in immunology · 2022Article
- The Immunogenetics of Autoimmune Blistering Diseases.Advances in experimental medicine and biology · 2022Review
- Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction.Nature communications · 2020Article
- Common Denominators in the Immunobiology of IgG4 Autoimmune Diseases: What Do Glomerulonephritis, Pemphigus Vulgaris, Myasthenia Gravis, Thrombotic Thrombocytopenic Purpura and Autoimmune Encephalitis Have in Common?Frontiers in immunology · 2020Review
- Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians.PLoS genetics · 2019Article
- Pemphigus: a Comprehensive Review on Pathogenesis, Clinical Presentation and Novel Therapeutic Approaches.Clinical reviews in allergy & immunology · 2018Review
- Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein Reactivity.Frontiers in immunology · 2018Article
- Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.Endocrinology · 2017Article
- Setting the target for pemphigus vulgaris therapy.JCI insight · 2017Review
- Identification of the core regulators of the HLA I-peptide binding process.Scientific reports · 2017Article
- A reciprocal HLA-Disease Association in Rheumatoid Arthritis and Pemphigus Vulgaris.Frontiers in bioscience (Landmark edition) · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Human T-cell-mediated autoimmune diseases are genetically linked to particular alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4 (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues (DR beta 67, 70, and 71). The disease is caused by autoantibodies against desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding motif, seven candidate peptides of the DG autoantigen were identified. T cells from four PV patients with active disease responded to one of these DG peptides (residues 190-204); two patients also responded to DG-(206-220). T-cell clones specific for DG-(190-204) secreted high levels of interleukins 4 and 10, indicating that they may be important in triggering the production of DG-specific autoantibodies. The DG-(190-204) peptide was presented by the disease-linked DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries a positive charge at the P4 position, was due to the negatively charged residues of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide binding site therefore appears to be a critical determinant of MHC-linked susceptibility to PV and rheumatoid arthritis.
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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.