ArticleFrontiers in endocrinology2021
Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors.
Article in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Heterogeneity between insulin and proinsulin in the potency for insulin autoantibodies in newly diagnosed type 1 diabetes children.Clinical and experimental immunology · 2026Article
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- T cell and autoantibody recognition of nucleus-associated islet autoantigens in individuals with type 1 diabetes.Diabetologia · 2025Article
- Immunopeptidomics for autoimmunity: unlocking the chamber of immune secrets.NPJ systems biology and applications · 2025Review
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes.Nature communications · 2024Article
- Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.Nature communications · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle.Frontiers in immunology · 2024Review
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas.Cell metabolism · 2023Review
- Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.Seminars in immunology · 2023Review
- Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.Frontiers in immunology · 2023Article
- Temporal development of T cell receptor repertoires during childhood in health and disease.JCI insight · 2022Article
- Guidelines for standardizing T-cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes.European journal of immunology · 2022Article
- Environmental Triggering of Type 1 Diabetes Autoimmunity.Frontiers in endocrinology · 2022Review
- Insulin B-chain hybrid peptides are agonists for T cells reactive to insulin B:9-23 in autoimmune diabetes.Frontiers in immunology · 2022Article
- Human islet T cells are highly reactive to preproinsulin in type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proinsulin is an abundant protein that is selectively expressed by pancreatic beta cells and has been a focus for development of antigen-specific immunotherapies for type 1 diabetes (T1D). In this study, we sought to comprehensively evaluate reactivity to preproinsulin by CD4 T cells originally isolated from pancreatic islets of organ donors having T1D. We analyzed 187 T cell receptor (TCR) clonotypes expressed by CD4 T cells obtained from six T1D donors and determined their response to 99 truncated preproinsulin peptide pools, in the presence of autologous B cells. We identified 14 TCR clonotypes from four out of the six donors that responded to preproinsulin peptides. Epitopes were found across all of proinsulin (insulin B-chain, C-peptide, and A-chain) including four hot spot regions containing peptides commonly targeted by TCR clonotypes derived from multiple T1D donors. Of importance, these hot spots overlap with peptide regions to which CD4 T cell responses have previously been detected in the peripheral blood of T1D patients. The 14 TCR clonotypes recognized proinsulin peptides presented by various HLA class II molecules, but there was a trend for dominant restriction with HLA-DQ, especially T1D risk alleles DQ8, DQ2, and DQ8-trans. The characteristics of the tri-molecular complex including proinsulin peptide, HLA-DQ molecule, and TCR derived from CD4 T cells in islets, provides an essential basis for developing antigen-specific biomarkers as well as immunotherapies.
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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.