ArticleClinical and experimental immunology2009
The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes.
Article in Clinical and experimental immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes.Diabetes · 2011Trial
- Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4PNAS nexus · 2024Article
- A minority of proliferating human CD4Frontiers in immunology · 2024Article
- Insulin B-chain hybrid peptides are agonists for T cells reactive to insulin B:9-23 in autoimmune diabetes.Frontiers in immunology · 2022Article
- Proinsulin-specific T-cell responses correlate with estimated c-peptide and predict partial remission duration in type 1 diabetes.Clinical & translational immunology · 2021Article
- Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Transgenic substitution with Greater Amberjack Seriola dumerili fish insulin 2 in NOD mice reduces beta cell immunogenicity.Scientific reports · 2019Article
- Proinsulin C-peptide is an autoantigen in people with type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Deciphering the Pathogenesis of Human Type 1 Diabetes (T1D) by Interrogating T Cells from the "Scene of the Crime".Current diabetes reports · 2017Review
- The cellular redox environment alters antigen presentation.The Journal of biological chemistry · 2014Article
- Advances in the cellular immunological pathogenesis of type 1 diabetes.Journal of cellular and molecular medicine · 2014Review
- Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9-23 epitope and involves functional epitope spreading.Journal of autoimmunity · 2012Article
- Extraction of tissue antigens for functional assays.Journal of visualized experiments : JoVE · 2012Article
- Posttranslational modifications of proteins in type 1 diabetes: the next step in finding the cure?Diabetes · 2012Article
- Pathogenic mechanisms in type 1 diabetes: the islet is both target and driver of disease.The review of diabetic studies : RDS · 2012Review
- Etiopathogenesis of insulin autoimmunity.Anatomy research international · 2012Article
- Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes.Clinical and experimental immunology · 2010Review
- The anti-insulin trimolecular complex in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2010Review
- Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes.Nature reviews. Immunology · 2010Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes (T1D) is caused by T cell-mediated destruction of the pancreatic insulin-producing beta cells. While the role of CD4(+) T cells in the pathogenesis of T1D is accepted widely, the epitopes recognized by pathogenic human CD4(+) T cells remain poorly defined. None the less, responses to the N-terminal region of the insulin A-chain have been described. Human CD4(+) T cells from the pancreatic lymph nodes of subjects with T1D respond to the first 15 amino acids of the insulin A-chain. We identified a human leucocyte antigen-DR4-restricted epitope comprising the first 13 amino acids of the insulin A-chain (A1-13), dependent upon generation of a vicinal disulphide bond between adjacent cysteines (A6-A7). Here we describe the analysis of a CD4(+) T cell clone, isolated from a subject with T1D, which recognizes a new HLR-DR4-restricted epitope (KRGIVEQCCTSICS) that overlaps the insulin A1-13 epitope. This is a novel epitope, because the clone responds to proinsulin but not to insulin, T cell recognition requires the last two residues of the C-peptide (Lys, Arg) and recognition does not depend upon a vicinal disulphide bond between the A6 and A7 cysteines. The finding of a further CD4(+) T cell epitope in the N-terminal A-chain region of human insulin underscores the importance of this region as a target of CD4(+) T cell responses in human T1D.
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