Epitopes described in "CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer."

Reference
Article Authors:Kristin V Tarbell; Mark Lee; Erik Ranheim; Cheng Chi Chao; Maija Sanna; Seon-Kyeong Kim; Peter Dickie; Luc Teyton; Mark Davis; Hugh McDevitt
Article Title:CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer.
Reference Detail
Reference ID:1007507
Abstract:Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286-300 (p286) of GAD65. These mice have GAD65-specific CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286-300-specific T cells have disease protective capacity and are not pathogenic.
Affiliations:Program in Immunology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Date:2002
Reference Type:Literature
PubMed ID:12186840
Journal:J Exp Med
Journal Volume:196
Article Pages:481-92
Journal ISSN:0022-1007
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@21f7147a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@64616701;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@36b1a623;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@49125fe2;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@555513e8;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@448e101c;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4ac3c16d;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@79d00173;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@470f637f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@434d4b4b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@78a4b72;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@85f2d3c;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2092c26f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@31b161e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@67490d29
Article MeSH List:Animals; Antigens, CD; Antigens, Differentiation(genetics); CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); CTLA-4 Antigen; Cell Division; Cytokines(biosynthesis); Diabetes Mellitus(immunology); Epitopes, T-Lymphocyte(immunology); Gene Expression; Glutamate Decarboxylase(immunology); Immunoconjugates; Isoenzymes(immunology); Mice; Mice, Inbred NOD; Mice, Transgenic; Peptides(immunology); Receptors, Antigen, T-Cell, alpha-beta(genetics; immunology); Receptors, Interleukin-2
Curation Last Updated:2015-01-17 21:53:50