Mapping the epitope in Epstein Barr Virus nuclear antigen-1 that elicits cross-reactivity with dsDNA (101.43)

Abstract Several studies have shown an association between Systemic Lupus Erythematosus (SLE) and the Epstein Barr Virus (EBV). Our laboratory recently demonstrated that BALB/c mice injected with the major EBV nuclear antigen, EBNA-1, developed antibodies to EBNA-1 that cross-react with double stranded DNA (dsDNA). We generated monoclonal antibodies (MAbs) to EBNA-1 from EBNA-1 injected mice and demonstrated by anti-dsDNA ELISA, dsDNA affinity columns, and Crithidia luciliae assays, that these antibodies cross-react with dsDNA. Studies are underway to determine the pathogenicity of these MAbs. We have been mapping the epitope in EBNA-1 that serves as a peptide mimotope for dsDNA. We now demonstrate that the mimotope is contained within the carboxyl region of the EBNA-1 protein, between amino acids 459 and 607. This region contains well-defined secondary structure, which suggests that the basis for the cross-reactivity with dsDNA could be due to a conformational epitope in EBNA-1. Studies are in progress to further map this cross-reactive epitope. Identification of this epitope may help in designing diagnostic and therapeutic strategies that can mask the epitope from the immune system following EBV infection and thereby prevent the development of antibodies that cross-react with dsDNA.