ArticleMolecular immunology2014
γδ T cells recognize the insulin B:9-23 peptide antigen when it is dimerized through thiol oxidation.
Article in Molecular immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Low immunogenicity of insulin efsitora alfa in participants with type 1 and type 2 diabetes mellitus.Diabetes, obesity & metabolism · 2026Pooled it
- Oxidative Post-Translational Modifications of Insulin in Type 1 Diabetes Autoimmunity.Immunological reviews · 2026Review
- γδ T cells in diabetes mellitus: dual roles and therapeutic implications.Frontiers in immunology · 2025Review
- The role of oxidative post-translational modifications in type 1 diabetes pathogenesis.Frontiers in immunology · 2025Review
- Autoantibody and T cell responses to oxidative post-translationally modified insulin neoantigenic peptides in type 1 diabetes.Diabetologia · 2023Article
- A Distinctive γδ T Cell Repertoire in NOD Mice Weakens Immune Regulation and Favors Diabetic Disease.Biomolecules · 2022Article
- Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions.Cellular & molecular immunology · 2020Review
- γδ TCR ligands: the quest to solve a 500-million-year-old mystery.Nature immunology · 2019Review
- A Special Connection between γδ T Cells and Natural Antibodies?Archivum immunologiae et therapiae experimentalis · 2016Review
- The T cell antigen receptor: the Swiss army knife of the immune system.Clinical and experimental immunology · 2015Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The insulin peptide B:9-23 is a natural antigen in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). In addition to αβ T cells and B cells, γδ T cells recognize the peptide and infiltrate the pancreatic islets where the peptide is produced within β cells. The peptide contains a cysteine in position 19 (Cys19), which is required for the γδ but not the αβ T cell response, and a tyrosine in position 16 (Tyr16), which is required for both. A peptide-specific mAb, tested along with the T cells, required neither of the two amino acids to bind the B:9-23 peptide. We found that γδ T cells require Cys19 because they recognize the peptide antigen in an oxidized state, in which the Cys19 thiols of two peptide molecules form a disulfide bond, creating a soluble homo-dimer. In contrast, αβ T cells recognize the peptide antigen as a reduced monomer, in complex with the MHCII molecule I-A(g7). Unlike the unstructured monomeric B:9-23 peptide, the γδ-stimulatory homo-dimer adopts a distinct secondary structure in solution, which differs from the secondary structure of the corresponding portion of the native insulin molecule. Tyr16 is required for this adopted structure of the dimerized insulin peptide as well as for the γδ response to it. This observation is consistent with the notion that γδ T cell recognition depends on the secondary structure of the dimerized insulin B:9-23 antigen.
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Registered trials
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