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

Coxsackie B Viruses (CBV) have been indicated as environmental triggers ini tiating autoimmune destruction of insulin-producing pancreatic p-cells, and molecular mimicry might be the mechanism. A prime candidate for inducing c ross-reactive immune responses is a homology sequence, PEVKEK, found both i n CBV4 2C protein and in GAD65. To characterize the CBV4-specific T-cell ep itopes, overlapping peptides covering the 2C protein were synthesized and C BV4-specific T-cell lines were established from healthy and diabetic subjec ts. 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 de tected. Peptide p4, which included the PEVKEK sequence, contained an HLA-DR 1-restricted T-cell epitope. Three randomly selected CBV4-specific T-cell l ines, which responded to peptide p4, failed to recognize GAD65 protein or G AD65 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-c ell epitope. However, presentation of this epitope in the context of neutra l HLA-DR1 allele does not support its role in pathogenesis of type 1 diabet es. (C) 2001 Academic Press.