ArticleProceedings of the National Academy of Sciences of the United States of America2021
T-cell responses to hybrid insulin peptides prior to type 1 diabetes development.
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. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Beta Cell Stress to Epitope Diversification: Post-Translationally Modified Antigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Hybrid Insulin Peptides as Antigens and Tolerogens for Pathogenic T Cells in Autoimmune Diabetes.Immunological reviews · 2026Review
- Unbiased discovery of autoreactive type 1 diabetes T-cell receptors that bind specific hybrid insulin peptides.Research square · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Antigen-specific immunotherapy with a CD4Nature communications · 2026Article
- TCR2HLA: Calibrated inference of HLA genotypes from TCR repertoires enables identification of immunologically relevant metaclonotypes.PLoS computational biology · 2026Article
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Strategic Reduction of Hybrid Insulin Peptide Formation Significantly Delays Diabetes Onset in NOD Mice.Diabetes · 2026Article
- TCR2HLA: calibrated inference of HLA genotypes from TCR repertoires enables identification of immunologically relevant metaclonotypes.bioRxiv : the preprint server for biology · 2025Article
- Novel T-Cell Reactivities to Hybrid Insulin Peptides in Islet Autoantibody-Positive At-Risk Individuals.Diabetes · 2025Article
- Autoimmune Type 1 Diabetes: An Early Approach Appraisal for Spain by the AGORA Diabetes Collaborative Group.Journal of clinical medicine · 2025Review
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4PNAS nexus · 2024Article
- Type 1 diabetes: immune pathology and novel therapeutic approaches.Diabetology international · 2024Review
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes.Diabetologia · 2024Review
- Mapping of a hybrid insulin peptide in the inflamed islet β-cells from NOD mice.Frontiers in immunology · 2024Article
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
T-cell responses to posttranslationally modified self-antigens are associated with many autoimmune disorders. In type 1 diabetes, hybrid insulin peptides (HIPs) are implicated in the T-cell-mediated destruction of insulin-producing β-cells within pancreatic islets. The natural history of the disease is such that it allows for the study of T-cell reactivity prior to the onset of clinical symptoms. We hypothesized that CD4 T-cell responses to posttranslationally modified islet peptides precedes diabetes onset. In a cohort of genetically at-risk individuals, we measured longitudinal T-cell responses to native insulin and hybrid insulin peptides. Both proinflammatory (interferon-γ) and antiinflammatory (interluekin-10) cytokine responses to HIPs were more robust than those to native peptides, and the ratio of such responses oscillated between pro- and antiinflammatory over time. However, individuals who developed islet autoantibodies or progressed to clinical type 1 diabetes had predominantly inflammatory T-cell responses to HIPs. Additionally, several HIP T-cell responses correlated to worsening measurements of blood glucose, highlighting the relevance of T-cell responses to posttranslationally modified peptides prior to autoimmune disease development.
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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.