ArticleDiabetes2012
Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill β-cells.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 112 citations in OpenAlex.
- Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes.The Journal of clinical investigation · 2018Trial
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Beta cell reactivity defines disease-relevant pancreatic CD8 T cells in type 1 diabetes.bioRxiv : the preprint server for biology · 2026Article
- Design of solubly expressed miniaturized SMART MHCs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Immunopeptidomics for autoimmunity: unlocking the chamber of immune secrets.NPJ systems biology and applications · 2025Review
- Implantation of Islets Co-Seeded with Tregs in a Novel Biomaterial Reverses Diabetes in the NOD Mouse Model.Tissue engineering and regenerative medicine · 2025Article
- Oral tolerogenic vaccine combined with gastrin restores immune tolerance and beta-cell function in NOD mice with Type 1 diabetes.Frontiers in immunology · 2025Article
- HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.The Journal of clinical investigation · 2024Article
- Microbial mimics supersize the pathogenic self-response.The Journal of clinical investigation · 2024Article
- High Resolution HLA-A, HLA-B, and HLA-C Allele Frequencies in Romanian Hematopoietic Stem Cell Donors.International journal of molecular sciences · 2024Article
- How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanism of Action of OralVaccines · 2024Article
- Pancreatic β cell derived extracellular vesicles containing surface preproinsulin are involved in glucose stimulated insulin secretion.Life sciences · 2024Article
- The Role of Aminopeptidase ERAP1 in Human Pathology-A Review.Current issues in molecular biology · 2024Review
- The role of islet autoantigen-specific T cells in the onset and treatment of type 1 diabetes mellitus.Frontiers in immunology · 2024Review
- Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.EClinicalMedicine · 2024Article
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
Type 1 diabetes results from T cell-mediated β-cell destruction. The HLA-A*24 class I gene confers significant risk of disease and early onset. We tested the hypothesis that HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T cells (CTLs). Surrogate β-cell lines secreting proinsulin and expressing HLA-A24 were generated and their peptide ligandome examined by mass spectrometry to discover naturally processed and HLA-A24-presented PPI epitopes. A novel PPI epitope was identified and used to generate HLA-A24 tetramers and examine the frequency of PPI-specific T cells in new-onset HLA-A*24(+) patients and control subjects. We identified a novel naturally processed and HLA-A24-presented PPI signal peptide epitope (PPI(3-11); LWMRLLPLL). HLA-A24 tetramer analysis reveals a significant expansion of PPI(3-11)-specific CD8 T cells in the blood of HLA-A*24(+) recent-onset patients compared with HLA-matched control subjects. Moreover, a patient-derived PPI(3-11)-specific CD8 T-cell clone shows a proinflammatory phenotype and kills surrogate β-cells and human HLA-A*24(+) islet cells in vitro. These results indicate that the type 1 diabetes susceptibility molecule HLA-A24 presents a naturally processed PPI signal peptide epitope. PPI-specific, HLA-A24-restricted CD8 T cells are expanded in patients with recent-onset disease. Human islet cells process and present PPI(3-11), rendering themselves targets for CTL-mediated killing.
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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.