title: Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus.
abstract: OBJECTIVE
  To examine the cross-reaction between viral and beta-cell protein determinants and to further understand the potential role of this mechanism in Type I (insuline-dependent) diabetes mellitus.
  
  
  METHODS
  Immune responses to a panel of 28 viral and beta-cell protein peptides representing selected sequences of rubella virus (RV), Coxsackie virus, human 38 KDa31G and glutamic acid decarboxylase (GAD 65 and 67) proteins in proliferation or cytotoxicity assays have been studied using uncloned and cloned T-cell cohorts from a group of 60 Type I diabetic patients.
  
  
  RESULTS
  Peptide GAD65(252-266) induced the responses of patients with recent onset diabetes in proliferation assays at the highest frequency (77%), whereas GAD67(212-226) stimulated the cellular responses at the highest rate (61%) in patients with late-onset diabetes. RVE1(157-176) was recognised by all groups of patients at the highest frequency and the largest amplitude among the viral peptides tested. T-cell clones specific to GAD65(252-266), GAD65(274-286) or GAD67(212-226) were tested in cytotoxicity assays for their responses to rubella virus peptides. Each of these T-cell clones cross-reacted with two to four rubella virus peptides, including RVE1(157-176) and RVE2(87-107). Analysis of the sequences of cross-reactive viral and glutamic acid decarboxylase antigens showed that these epitopes shared similar peptide binding motifs to HLA DR3/DR4. There is a statistically significant correlation between the response amplitude of patient's peripheral blood mononuclear cells to RVE1(157-176), RVE2(87-107) and GAD65(274-286) in patients with recent onset diabetes, and to RVE1(157-176) and GAD67(212-226) in patients with late onset diabetes.
  
  
  CONCLUSIONS
  Cross-reactive glutamic acid decarboxylase and rubella virus determinants identified by T-cell clones were also recognised at high frequencies by general T-cell populations of Type I diabetic patients.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Ou
authors.forename: L A
authors.initials: LA
authors.lastname: Mitchell
authors.forename: D L
authors.initials: DL
authors.lastname: Metzger
authors.forename: S
authors.initials: S
authors.lastname: Gillam
authors.forename: A J
authors.initials: AJ
authors.lastname: Tingle
mesh_terms: D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004770:Enterovirus / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012412:Rubella virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D007527:Isoenzymes; D010446:Peptide Fragments; D014764:Viral Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2