Epitopes described in "Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes."

Reference
Article Authors:M A Atkinson; M A Bowman; L Campbell; B L Darrow; D L Kaufman; N K Maclaren
Article Title:Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes.
Reference Detail
Reference ID:1014526
Abstract:Insulin-dependent diabetes (IDD) results from the autoimmune destruction of the insulin-producing pancreatic beta cells. Autoreactive T-lymphocytes are thought to play a pivotal role in the pathogenesis of IDD; however, the target antigens of these cells, as well as the inductive events in the disease, are unclear. PBMC in persons with or at increased risk for IDD show elevated reactivity to the beta cell enzyme glutamate decarboxylase (GAD). To identify the T-lymphocyte-reactive determinants of GAD, an overlapping set of synthetic peptides was used to stimulate the PBMC from these individuals, PBMC responsiveness to GAD peptides was not restricted to those with IDD, and a number of peptides elicited responses in PBMC. However, the major determinant of GAD recognized by persons at increased risk for IDD was amino acids 247-279, a region which has significant sequence similarity to the P2-C protein of Coxsackie B virus (47% of 15 increased risk [islet cell autoantibody-positive relatives]; 25% of 16 newly diagnosed IDD patients; and 0% of 13 healthy control subjects). Responses to tetanus and insulin antigens were not different between the study groups. In addition, PBMC from individuals responding to GAD peptides within 247-279 also responded to a Coxsackie viral peptide (i.e., P2-C amino acids 32-47), an observation supporting potential molecular mimicry in this immune response. Although the role of environmental agents in the pathogenesis of the disease remains unclear, these cellular immunological findings support the epidemiological evidence suggesting an inductive role for enteroviruses like Coxsackie B in the autoimmunity underlying IDD.
Date:1994
Reference Type:Literature
PubMed ID:7962558
Journal:J Clin Invest
Journal Volume:94
Article Pages:2125-9
Journal ISSN:0021-9738
Article Chemical List:Antibodies, Viral;Peptide Fragments;Glutamate Decarboxylase
Article MeSH List:Adolescent; Adult; Amino Acid Sequence; Antibodies, Viral(blood); Child; Diabetes Mellitus, Type 1(immunology; virology); Enterovirus(immunology); Female; Glutamate Decarboxylase(immunology); Humans; Immunity, Cellular; Male; Middle Aged; Molecular Sequence Data; Peptide Fragments(immunology)
Curation Last Updated:2014-10-03 21:31:12