ArticleProceedings of the National Academy of Sciences of the United States of America2014
Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 119 citations in OpenAlex.
- Hybrid Insulin Peptides as Antigens and Tolerogens for Pathogenic T Cells in Autoimmune Diabetes.Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- PepGen: conditional generation of peptides for MHC binding.Bioinformatics (Oxford, England) · 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
- 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
- Clinical applications and methodology updates in HLA typing.BMC immunology · 2026Review
- A universal platform for simultaneous TCRα/β removal enables safer and more potent TCR therapies and autoimmune modeling.bioRxiv : the preprint server for biology · 2026Article
- TCR-Based Antigen-Specific Therapy for Type 1 Diabetes Mellitus: From Editing Autoreactive Clones to Tolerance Induction.International journal of molecular sciences · 2025Review
- Combined Adaptive Immune Mechanisms Mediate Cardiac Injury After COVID-19 Vaccination.Circulation · 2025Article
- Impact of Parabacteroides distasonis colonization on host microbiome, metabolome, immunity, and diabetes onset.Journal of molecular endocrinology · 2025Article
- Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.Nature cardiovascular research · 2025Review
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- The insulin secretory granule is a hotspot for autoantigen formation in type 1 diabetes.Diabetologia · 2024Review
- Antigen-specific T cell responses in autoimmune diabetes.Frontiers in immunology · 2024Review
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells.Science translational medicine · 2023Article
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
- Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65Frontiers in immunology · 2023Article
- Genetically engineered CD80-pMHC-harboring extracellular vesicles for antigen-specific CD4Frontiers in bioengineering and biotechnology · 2023Article
- Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes.Frontiers in immunology · 2023Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Previous studies in type 1 diabetes (T1D) in the nonobese diabetic mouse demonstrated that a crucial insulin epitope (B:9-23) is presented to diabetogenic CD4 T cells by IA(g7) in a weakly bound register. The importance of antigenic peptides with low-affinity HLA binding in human autoimmune disease remains less clear. The objective of this study was to investigate T-cell responses to a low-affinity self-epitope in subjects with T1D. HLA-DQ8 tetramers loaded with a modified insulin peptide designed to improve binding the low-affinity register were used to visualize T-cell responses following in vitro stimulation. Positive responses were only detectable in T1D patients. Because the immunogenic register of B:9-23 presented by DQ8 has not been conclusively demonstrated, T-cell assays using substituted peptides and DQ8 constructs engineered to express and present B:9-23 in fixed binding registers were used to determine the immunogenic register of this peptide. Tetramer-positive T-cell clones isolated from T1D subjects that responded to stimulation by B:11-23 peptide and denatured insulin protein were conclusively shown to recognize B:11-23 bound to HLA-DQ8 in the low-affinity register 3. These T cells also responded to homologous peptides derived from microbial antigens, suggesting that their initial priming could occur via molecular mimicry. These results are in accord with prior observations from the nonobese diabetic mouse model, suggesting a mechanism shared by mouse and man through which T cells that recognize a weakly bound peptide can circumvent tolerance mechanisms and play a role in the initiation of autoimmune diseases, such as T1D.
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