ArticleProceedings of the National Academy of Sciences of the United States of America1998
T cell epitopes of insulin defined in HLA-DR4 transgenic mice are derived from preproinsulin and proinsulin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 113 citations in OpenAlex.
- Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65Frontiers in immunology · 2023Article
- A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.Frontiers in immunology · 2021Article
- Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells.Frontiers in endocrinology · 2021Review
- Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools.Frontiers in immunology · 2020Review
- Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space.Frontiers in immunology · 2019Article
- Heterogeneity of B Cell Functions in Stroke-Related Risk, Prevention, Injury, and Repair.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Review
- T cell epitope mapping of JC polyoma virus-encoded proteome reveals reduced T cell responses in HLA-DRB1*04:01+ donors.Journal of virology · 2013Article
- Islet autoantigens: structure, function, localization, and regulation.Cold Spring Harbor perspectives in medicine · 2012Review
- T cell recognition of autoantigens in human type 1 diabetes: clinical perspectives.Clinical & developmental immunology · 2011Review
- Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.Genes and immunity · 2010Article
- Differential responses to Smith D autoantigen by mice with HLA-DR and HLA-DQ transgenes: dominant responses by HLA-DR3 transgenic mice with diversification of autoantibodies to small nuclear ribonucleoprotein, double-stranded DNA, and nuclear antigens.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes.Clinical and experimental immunology · 2009Article
- Myelin-reactive type B T cells and T cells specific for low-affinity MHC-binding myelin peptides escape tolerance in HLA-DR transgenic mice.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis.American journal of human genetics · 2008Article
- Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice.Journal of autoimmunity · 2008Article
- Insulin as an autoantigen in NOD/human diabetes.Current opinion in immunology · 2008Review
- Translational mini-review series on type 1 diabetes: Systematic analysis of T cell epitopes in autoimmune diabetes.Clinical and experimental immunology · 2007Review
- Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.Clinical immunology (Orlando, Fla.) · 2006Article
- DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Approximately one-half of Caucasians with newly diagnosed insulin-dependent diabetes mellitus (IDDM) have autoantibodies to insulin, and the majority of those express the HLA-DR4 genotype [Ziegler, R., Alper, C. A., Awdeh, Z. L., Castano, L., Brink, S. J., Soeldner, J. S., Jackson, R. A. & Eisenbarth, G. S. (1991) Diabetes 40, 709-714]. However, it has been difficult to demonstrate T cell proliferative responses to human insulin in IDDM patients [Durinovic-Bello, I., Hummel, M. & Ziegler, A. G. (1996) Diabetes 45, 795-800]. We have immunized transgenic mice expressing the susceptible HLA-DR (alpha1*0101,beta1*0401) (hereafter called DRB1*0401) and human CD4 molecules on a murine major histocompatibility complex class II null background, with human preproinsulin (PPI), proinsulin (PI), and insulin and derived large panels of T cell hybridomas to determine the immunogenic epitopes of these proteins. These results show that the prohormones PI or PPI carry the major immunogenic T cell epitope in the DRB1*0401 transgenic mice. The PPI/PI immunodominant epitope LALEGSLQK was localized at the C-peptide/A-chain junction. This T cell epitope PPI/PI LALEGSLQK is unusual because, normally, it is proteolytically destroyed during the maturation of the insulin molecule. Additionally, this T cell epitope is both processed and presented by human DRB1*0401-positive Epstein-Barr virus transformed B cells, and it can also stimulate T cells from the peripheral blood of HLA-DR4-positive patients with type 1 diabetes. These findings may partly explain why susceptibility to type 1 diabetes is associated with HLA-DR4-positive individuals and why T cell responses to the mature insulin protein are rarely detected in IDDM patients.
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