ArticleProceedings of the National Academy of Sciences of the United States of America2011
Specificity and detection of insulin-reactive CD4+ T cells in type 1 diabetes in the nonobese diabetic (NOD) mouse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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122 citing papers in PubMed, 139 citations in OpenAlex.
- Identification of multiple public TCR repertoires in chronic beryllium disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- A novel region of the insulin B9-23 sequence is targeted by a HIP-reactive diabetogenic T cell clone.Frontiers in immunology · 2026Article
- Autoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes.Diabetes · 2025Article
- Cellular therapies in rheumatic and musculoskeletal diseases.Journal of translational autoimmunity · 2025Review
- CD4Immunity · 2024Article
- 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
- Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Antigen-specific T cell responses in autoimmune diabetes.Frontiers in immunology · 2024Review
- Soluble antigen arrays provide increased efficacy and safety over free peptides for tolerogenic immunotherapy.Frontiers in immunology · 2024Article
- Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.Frontiers in immunology · 2024Review
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Applications of Genome-Editing Technologies for Type 1 Diabetes.International journal of molecular sciences · 2023Review
- Tregs with an MHC class II peptide-specific chimeric antigen receptor prevent autoimmune diabetes in mice.The Journal of clinical investigation · 2023Article
- HLA-DR3 mediated CD4 T cell response against GAD65 in type 1 diabetes patients.Journal of diabetes · 2023Article
- Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes.bioRxiv : the preprint server for biology · 2023Article
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
- Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes.Frontiers in immunology · 2023Article
- The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer.Frontiers in immunology · 2023Review
- Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8Frontiers in immunology · 2023Article
62 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
Funding
Abstract
In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9-23) is a major target for pathogenic CD4(+) T cells. However, there is no consensus on the relative importance of the various positions or "registers" this peptide can take when bound in the groove of the NOD MHCII molecule, IA(g7). This has hindered structural studies and the tracking of the relevant T cells in vivo with fluorescent peptide-MHCII tetramers. Using mutated B:9-23 peptides and methods for trapping the peptide in particular registers, we show that most, if not all, NOD CD4(+) T cells react to B:9-23 bound in low-affinity register 3. However, these T cells can be divided into two types depending on whether their response is improved or inhibited by substituting a glycine for the B:21 glutamic acid at the p8 position of the peptide. On the basis of these findings, we constructed a set of fluorescent insulin-IA(g7) tetramers that bind to most insulin-specific T-cell clones tested. A mixture of these tetramers detected a high frequency of B:9-23-reactive CD4(+) T cells in the pancreases of prediabetic NOD mice. Our data are consistent with the idea that, within the pancreas, unique processing of insulin generates truncated peptides that lack or contain the B:21 glutamic acid. In the thymus, the absence of this type of processing combined with the low affinity of B:9-23 binding to IA(g7) in register 3 may explain the escape of insulin-specific CD4(+) T cells from the mechanisms that usually eliminate self-reactive T cells.
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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.