ArticleThe Journal of experimental medicine2005
The insulin A-chain epitope recognized by human T cells is posttranslationally modified.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- Low immunogenicity of insulin efsitora alfa in participants with type 1 and type 2 diabetes mellitus.Diabetes, obesity & metabolism · 2026Pooled it
- Citrullination and Deamidation in Type 1 Diabetes: Linking Beta Cell Stress to Neoantigen-Driven Autoimmunity.Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Oxidative Post-Translational Modifications of Insulin in Type 1 Diabetes Autoimmunity.Immunological reviews · 2026Review
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Unlocking beta cell health: The clinical potential of extracellular vesicles in type 1 diabetes.Clinical and translational medicine · 2026Review
- Strategic Reduction of Hybrid Insulin Peptide Formation Significantly Delays Diabetes Onset in NOD Mice.Diabetes · 2026Article
- A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes.Nature immunology · 2026Article
- Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.International journal of molecular sciences · 2025Review
- Article
- Antigen presentation of post-translationally modified peptides in major histocompatibility complexes.Immunology and cell biology · 2025Review
- The role of oxidative post-translational modifications in type 1 diabetes pathogenesis.Frontiers in immunology · 2025Review
- Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4PNAS nexus · 2024Article
- The insulin secretory granule is a hotspot for autoantigen formation in type 1 diabetes.Diabetologia · 2024Review
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- A minority of proliferating human CD4Frontiers in immunology · 2024Article
- Assessing the immunogenicity risk of salmon calcitonin peptide impurities usingFrontiers in pharmacology · 2024Article
- Understanding Islet Autoantibodies in Prediction of Type 1 Diabetes.Journal of the Endocrine Society · 2023Review
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- Identification of Autoantibodies to a Hybrid Insulin Peptide in Type 1 Diabetes.Diagnostics (Basel, Switzerland) · 2023Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The autoimmune process that destroys the insulin-producing pancreatic beta cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T cells that recognize the proximal A-chain of human insulin were identified recently in the pancreatic lymph nodes of subjects who had T1D. To investigate the specificity of proinsulin-specific T cells in T1D, we isolated human CD4(+) T cell clones to proinsulin from the blood of a donor who had T1D. The clones recognized a naturally processed, HLA DR4-restricted epitope within the first 13 amino acids of the A-chain (A1-13) of human insulin. T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. CD4(+) T cell clones that recognized this epitope were isolated from an HLA DR4(+) child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4(+) donors. We define for the first time a novel posttranslational modification that is required for T cell recognition of the insulin A-chain in T1D.
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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.