ArticleClinical and experimental immunology2012
CD8 T cell autoreactivity to preproinsulin epitopes with very low human leucocyte antigen class I binding affinity.
Article in Clinical and experimental immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03369821 (Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes), which is not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)
Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Extracellular vesicles inherit lactate from aggregated MSCs to alleviate type 1 diabetes mellitus via HJournal of nanobiotechnology · 2026Article
- Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance.Endocrine reviews · 2025Review
- Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes.Frontiers in immunology · 2024Article
- IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.Diabetologia · 2023Article
- The need and benefit of immune monitoring to define patient and disease heterogeneity, mechanisms of therapeutic action and efficacy of intervention therapy for precision medicine in type 1 diabetes.Frontiers in immunology · 2023Article
- High-throughput and high-dimensional single-cell analysis of antigen-specific CD8Nature immunology · 2021Article
- Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nature reviews. Endocrinology · 2021Review
- 21-Hydroxylase-Specific CD8+ T Cells in Autoimmune Addison's Disease Are Restricted by HLA-A2 and HLA-C7 Molecules.Frontiers in immunology · 2021Article
- Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- A Novel Quantitative Approach to Staging and Assessing Recovery from Type 1 Diabetes Mellitus: The Type 1 Diabetes Mellitus Metabolic Recovery Index.International journal of molecular sciences · 2020Article
- Viral Hormones: Expanding Dimensions in Endocrinology.Endocrinology · 2019Review
- Low HLA binding of diabetes-associated CD8+ T-cell epitopes is increased by post translational modifications.BMC immunology · 2018Article
- Heterogeneity of circulating CD8 T-cells specific to islet, neo-antigen and virus in patients with type 1 diabetes mellitus.PloS one · 2018Article
- Autoreactive T cells in type 1 diabetes.The Journal of clinical investigation · 2017Review
- Type I Interferon Is a Catastrophic Feature of the Diabetic Islet Microenvironment.Frontiers in endocrinology · 2017Review
- Detection of vasostatin-1-specific CD8(+) T cells in non-obese diabetic mice that contribute to diabetes pathogenesis.Clinical and experimental immunology · 2016Article
- Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes.Diabetologia · 2016Article
- Solving the puzzle of autoimmunity: critical questions.F1000prime reports · 2015Review
- Article
- Progress in immune-based therapies for type 1 diabetes.Clinical and experimental immunology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Beta cells presenting islet epitopes are recognized and destroyed by autoreactive CD8 T cells in type 1 diabetes. These islet-specific T cells are believed to react with epitopes binding with high affinity to human leucocyte antigen (HLA) expressed on beta cells. However, this assumption might be flawed in case of islet autoimmunity. We evaluated T cell recognition of the complete array of preproinsulin (PPI) peptides with regard to HLA binding affinity and T cell recognition. In a comprehensive approach, 203 overlapping 9-10mer PPI peptides were tested for HLA-A2 binding and subjected to binding algorithms. Subsequently, a high-throughput assay was employed to detect PPI-specific T cells in patient blood, in which conditional HLA ligands were destabilized by ultraviolet irradiation and HLA molecules refolded with arrays of PPI peptides, followed by quantum-dot labelling and T cell staining. Analysis of patient blood revealed high frequencies of CD8 T cells recognizing very low HLA binding peptides. Of 28 peptides binding to HLA-A2, a majority was predicted not to bind. Unpredicted peptides bound mainly with low affinities. HLA binding affinity and immunogenicity may not correlate in autoimmunity. Algorithms used to predict high-affinity HLA peptide binders discount the majority of low-affinity HLA binding epitopes. Appreciation that peptides binding HLA with very low affinity can act as targets of autoreactive T cells may help to understand loss of tolerance and disease pathogenesis and possibly point to tissue-specific immune intervention targets.
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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.