Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM.
Virus infection has been proposed as an initiating factor in the aetiology of insulin-dependent diabetes mellitus (IDDM). We have examined lymphocyte proliferation to virus proteins which demonstrate sequence similarity to the beta-cell autoantigen glutamic acid decarboxylase (GAD)65. The magnitude and frequency of response to coxsackie B viruses and adenovirus in a T-cell proliferation assay was significantly higher in a group of recently diagnosed IDDM subjects than in non-diabetic control subjects. The frequency of positive response to the coxsackie B viruses was also significantly higher in IDDM subjects expressing the DRB 1*04 major histocompatibility complex (MHC) haplotype than the DRB 1*03 haplotype. There was no evidence that non-aspartate residue at position 57 of DQB 1 genes influenced virus responses in the IDDM group. The coxsackie homology was in amino acids 258-266 and the adenovirus homology was in amino acids 509-524 of GAD65. Both these regions are suspected to be T-cell epitopes in IDDM. These results indicate a disease and MHC class II association between coxsackie B virus infection and IDDM and an association between adenovirus infection and IDDM.
Jones
D B
DB
Department of Immunology, University of Liverpool, UK.
Crosby
I
I
D000256:Adenoviridae / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D015999:Multivariate Analysis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D006684:HLA-DR Antigens; D005968:Glutamate Decarboxylase