ArticleJournal of clinical immunology2004
T cells recognize multiple GAD65 and proinsulin epitopes in human type 1 diabetes, suggesting determinant spreading.
Article in Journal of clinical immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 54 citations in OpenAlex.
- Antigen-specific T cell responses in autoimmune diabetes.Frontiers in immunology · 2024Review
- Mechanisms governing bystander activation of T cells.Frontiers in immunology · 2024Review
- Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65Frontiers in immunology · 2023Article
- Circulating β cell-specific CD8Clinical and experimental immunology · 2020Article
- Natural T cell autoreactivity to melanoma antigens: clonally expanded melanoma-antigen specific CD8 + memory T cells can be detected in healthy humans.Cancer immunology, immunotherapy : CII · 2019Article
- Autoreactive T cells in type 1 diabetes.The Journal of clinical investigation · 2017Review
- T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes.Frontiers in endocrinology · 2017Review
- How frequently are predicted peptides actually recognized by CD8 cells?Cancer immunology, immunotherapy : CII · 2016Review
- Etiopathogenesis of insulin autoimmunity.Anatomy research international · 2012Article
- Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human disease.Seminars in immunopathology · 2011Review
- H-Y antibody titers are increased in unexplained secondary recurrent miscarriage patients and associated with low male : female ratio in subsequent live births.Human reproduction (Oxford, England) · 2010Article
- IFN-gamma and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes.Diabetologia · 2010Article
- Antigen-based therapy for the treatment of type 1 diabetes.Diabetes · 2009Article
- Molecular mechanisms of T-cell receptor and costimulatory molecule ligation/blockade in autoimmune disease therapy.Immunological reviews · 2009Review
- Detection of GAD65 autoreactive T-cells by HLA class I tetramers in type 1 diabetic patients.Journal of biomedicine & biotechnology · 2009Article
- Beta-cell mass and type 1 diabetes: going, going, gone?Diabetes · 2008Review
- Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetes.Journal of leukocyte biology · 2008Article
- Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery.Journal of clinical immunology · 2008Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Human type 1 diabetes is thought to be mediated by autoreactive T cells specific for antigens expressed by pancreatic beta cells. However, it is unclear which autoantigens and determinants thereof are the targets of the autoimmune attack. Using comprehensive peptide libraries that cover the entire sequence of two major candidate autoantigens, GAD65 and proinsulin, we measured the in vivo frequencies of peptide-specific, IFN-gamma-producing memory T cells in 27 diabetic patients, 14 high risk individuals, and 15 partially HLA-matched healthy controls. Compared to the controls, both a higher number of determinants on the islet cell antigens were recognized and the frequencies of peptide specific cells were increased in patients and high risk individuals. Inclusion of signal enhancing anti-CD28 antibody further accentuated this difference. Considerable heterogeneity in peptide recognition was seen even in DRB1*04, DQB1*0302 matched individuals. Unlike its peptides, the GAD protein antigen did not recall a T cell memory response. The highly heterogeneous recognition of a multitude of peptide determinants on both autoantigens, occurring in the absence of protein recognition, and the low functional avidity of the memory cells involved jointly suggest that the autoimmune T cell repertoire in human type 1 diabetes primarily targets cryptic determinants engaged by determinant spreading.
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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.