Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM

Diabetologia. 1996 Nov;39(11):1318-24. doi: 10.1007/s001250050576.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adenoviridae / immunology
  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Antigens, Viral / chemistry
  • Antigens, Viral / classification
  • Antigens, Viral / immunology*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology*
  • Enterovirus B, Human / immunology*
  • Glutamate Decarboxylase / chemistry
  • Glutamate Decarboxylase / immunology*
  • HLA-DR Antigens / immunology
  • Humans
  • Lymphocyte Activation
  • Multivariate Analysis
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Viral
  • HLA-DR Antigens
  • Glutamate Decarboxylase