Epitopes described in "Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes."

Article Authors:D L Kaufman; M Clare-Salzler; J Tian; T Forsthuber; G S Ting; P Robinson; M A Atkinson; E E Sercarz; A J Tobin; P V Lehmann
Article Title:Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes.
Reference Detail
Reference ID:1014512
Abstract:Insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice results from the T-lymphocyte-mediated destruction of the insulin-producing pancreatic beta-cells and serves as a model for human IDDM. Whereas a number of autoantibodies are associated with IDDM, it is unclear when and to what beta-cell antigens pathogenic T cells become activated during the disease process. We report here that a T-helper-1 (Th1) response to glutamate decarboxylase develops in NOD mice at the same time as the onset of insulitis. This response is initially limited to a confined region of glutamate decarboxylase, but later spreads intramolecularly to additional determinants. Subsequently, T-cell reactivity arises to other beta-cell antigens, consistent with intermolecular diversification of the response. Prevention of the spontaneous anti-glutamate decarboxylase response, by tolerization of glutamate decarboxylase-reactive T cells, blocks the development of T-cell autoimmunity to other beta-cell antigens, as well as insulitis and diabetes. Our data suggest that (1) glutamate decarboxylase is a key target antigen in the induction of murine IDDM; (2) autoimmunity to glutamate decarboxylase triggers T-cell responses to other beta-cell antigens, and (3) spontaneous autoimmune disease can be prevented by tolerization to the initiating target antigen.
Affiliations:Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles 90024.
Reference Type:Literature
PubMed ID:7694152
Journal Volume:366
Article Pages:69-72
Journal ISSN:0028-0836
Article Chemical List:Autoantigens;Epitopes;Glutamate Decarboxylase
Article MeSH List:Aging(immunology); Amino Acid Sequence; Animals; Autoantigens(immunology); Diabetes Mellitus, Type 1(immunology; pathology); Epitopes(immunology); Female; Glutamate Decarboxylase(immunology); Immunosuppression; Islets of Langerhans(immunology; pathology); Mice; Mice, Inbred NOD; Molecular Sequence Data; T-Lymphocytes, Helper-Inducer(immunology)
Curation Last Updated:2015-07-30 20:29:57