ArticleProceedings of the National Academy of Sciences of the United States of America2021
Human islet T cells are highly reactive to preproinsulin in type 1 diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 81 citations in OpenAlex.
- Immune dysregulation and stem-like CD8+ T cell enrichment in type 1 diabetes pancreatic lymph nodes.The Journal of clinical investigation · 2026Article
- Multiomics approaches reveal direct NF-κB p65 target genes in pancreatic islets during cytokine exposure and in type 1 diabetes.American journal of physiology. Endocrinology and metabolism · 2026Article
- Structural Remodeling of TCR-HLA-DQ8 Recognition by a β-Cell Stress-Associated C19S Insulin Neoepitope in Type 1 Diabetes.International journal of molecular sciences · 2026Article
- Generation of Regulatory T Cells Against Islet Neoantigen.European journal of immunology · 2026Article
- Structural Modulation and Binding of HLA-DQ8 by Cysteine-to-Serine Mutated Insulin Peptide: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- Aberrant immune regulation and enrichment of stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Quantitative V gene-targeted T cell receptor sequencing as a biomarker in type 1 diabetes.JCI insight · 2026Article
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Type 1 diabetesNPJ autoimmunity · 2026Article
- Limited efficacy of a therapeutic anti-CD40 monoclonal antibody to inhibit activated CD4 T cell autoimmunity in vitro.PloS one · 2026Article
- Proteogenomic Discovery of Novel Open Reading Frames With HLA Immune Presentation on Human β-Cells.Diabetes · 2025Article
- Explosive cytotoxicity of 'ruptoblasts' bridges hormonal surveillance and immune defense.bioRxiv : the preprint server for biology · 2025Article
- Article
- Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas.Journal for immunotherapy of cancer · 2025Article
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.EBioMedicine · 2025Article
- Tissue Resident and Infiltrating Immune Cells: Their Influence on the Demise of Beta Cells in Type 1 Diabetes.Biomolecules · 2025Review
- Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.Biomolecules · 2025Review
- Immunopeptidomics for autoimmunity: unlocking the chamber of immune secrets.NPJ systems biology and applications · 2025Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Cytotoxic CD8 T lymphocytes play a central role in the tissue destruction of many autoimmune disorders. In type 1 diabetes (T1D), insulin and its precursor preproinsulin are major self-antigens targeted by T cells. We comprehensively examined preproinsulin specificity of CD8 T cells obtained from pancreatic islets of organ donors with and without T1D and identified epitopes throughout the entire preproinsulin protein and defective ribosomal products derived from preproinsulin messenger RNA. The frequency of preproinsulin-reactive T cells was significantly higher in T1D donors than nondiabetic donors and also differed by individual T1D donor, ranging from 3 to over 40%, with higher frequencies in T1D organ donors with HLA-A*02:01. Only T cells reactive to preproinsulin-related peptides isolated from T1D donors demonstrated potent autoreactivity. Reactivity to similar regions of preproinsulin was also observed in peripheral blood of a separate cohort of new-onset T1D patients. These findings have important implications for designing antigen-specific immunotherapies and identifying individuals that may benefit from such interventions.
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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.