ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 73 citations in OpenAlex.
- Quantitative V gene-targeted T cell receptor sequencing as a biomarker in type 1 diabetes.JCI insight · 2026Article
- TCR-Based Antigen-Specific Therapy for Type 1 Diabetes Mellitus: From Editing Autoreactive Clones to Tolerance Induction.International journal of molecular sciences · 2025Review
- Impact of Parabacteroides distasonis colonization on host microbiome, metabolome, immunity, and diabetes onset.Journal of molecular endocrinology · 2025Article
- Deciphering Autoimmune Diseases: Unveiling the Diagnostic, Therapeutic, and Prognostic Potential of Immune Repertoire Sequencing.Inflammation · 2025Review
- Lymphedema pathogenesis involves antigen-driven expansion of CD4+ T cells in skin.Frontiers in immunology · 2025Article
- Article
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Monitoring islet specific immune responses in type 1 diabetes clinical immunotherapy trials.Frontiers in immunology · 2023Review
- The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer.Frontiers in immunology · 2023Review
- Temporal development of T cell receptor repertoires during childhood in health and disease.JCI insight · 2022Article
- A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Activation pathways that drive CD4Immunological reviews · 2022Review
- Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes.International journal of molecular sciences · 2022Review
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- A Novel Tolerogenic Antibody Targeting Disulfide-Modified Autoantigen Effectively Prevents Type 1 Diabetes in NOD Mice.Frontiers in immunology · 2022Article
- Insulin B-chain hybrid peptides are agonists for T cells reactive to insulin B:9-23 in autoimmune diabetes.Frontiers in immunology · 2022Article
- Enhancing Antigen Presentation and Inducing Antigen-Specific Immune Tolerance with Amphiphilic Peptides.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- T-cell responses to hybrid insulin peptides prior to type 1 diabetes development.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Certain class II MHC (MHCII) alleles in mice and humans confer risk for or protection from type 1 diabetes (T1D). Insulin is a major autoantigen in T1D, but how its peptides are presented to CD4 T cells by MHCII risk alleles has been controversial. In the mouse model of T1D, CD4 T cells respond to insulin B-chain peptide (B:9-23) mimotopes engineered to bind the mouse MHCII molecule, IA(g7), in an unfavorable position or register. Because of the similarities between IA(g7) and human HLA-DQ T1D risk alleles, we examined control and T1D subjects with these risk alleles for CD4 T-cell responses to the same natural B:9-23 peptide and mimotopes. A high proportion of new-onset T1D subjects mounted an inflammatory IFN-γ response much more frequently to one of the mimotope peptides than to the natural peptide. Surprisingly, the control subjects bearing an HLA-DQ risk allele also did. However, these control subjects, especially those with only one HLA-DQ risk allele, very frequently made an IL-10 response, a cytokine associated with regulatory T cells. T1D subjects with established disease also responded to the mimotope rather than the natural B:9-23 peptide in proliferation assays and the proliferating cells were highly enriched in certain T-cell receptor sequences. Our results suggest that the risk of T1D may be related to how an HLA-DQ genotype determines the balance of T-cell inflammatory vs. regulatory responses to insulin, having important implications for the use and monitoring of insulin-specific therapies to prevent diabetes onset.
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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.