Responses of coxsackievirus B4-specific T-cell lines to 2C protein-characterization of epitopes with special reference to the GAD65 homology region

Virology. 2001 May 25;284(1):131-41. doi: 10.1006/viro.2001.0917.

Abstract

Coxsackie B viruses (CBV) have been indicated as environmental triggers initiating autoimmune destruction of insulin-producing pancreatic beta-cells, and molecular mimicry might be the mechanism. A prime candidate for inducing cross-reactive immune responses is a homology sequence, PEVKEK, found both in CBV4 2C protein and in GAD65. To characterize the CBV4-specific T-cell epitopes, overlapping peptides covering the 2C protein were synthesized and CBV4-specific T-cell lines were established from healthy and diabetic subjects. The T-cell epitopes were dependent on the HLA-DR genotype of the T-cell donor, but no difference between diabetic and healthy subjects could be detected. Peptide p4, which included the PEVKEK sequence, contained an HLA-DR1-restricted T-cell epitope. Three randomly selected CBV4-specific T-cell lines, which responded to peptide p4, failed to recognize GAD65 protein or GAD65 peptides containing the PEVKEK sequence. We conclude that the CBV4 2C protein is strongly immunogenic for T-cells and PEVKEK is included in a T-cell epitope. However, presentation of this epitope in the context of neutral HLA-DR1 allele does not support its role in pathogenesis of type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology*
  • Cell Division
  • Cell Line
  • Child
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / virology
  • Enterovirus / genetics*
  • Enterovirus / immunology*
  • Epitope Mapping
  • Glutamate Decarboxylase / genetics*
  • HLA-DR1 Antigen / genetics
  • Humans
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / virology
  • Isoenzymes / genetics*
  • Molecular Mimicry
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / virology*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / pharmacology*

Substances

  • Carrier Proteins
  • Cytokines
  • HLA-DR1 Antigen
  • Isoenzymes
  • Viral Nonstructural Proteins
  • 2C protein, viral
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2