MOLECULAR-BASIS FOR ANTIBODY CROSS-REACTIVITY BETWEEN THE HEPATITIS-CVIRUS CORE PROTEIN AND THE HOST-DERIVED GOR PROTEIN

The presence of antibodies reactive to a recently cloned host-derived antigen GOR is highly correlated with the presence of antibodies to th e hepatitis C virus (HCV). We explored the molecular basis for this ob servation, and address the following question: are antibodies reactive with GOR(19-27) (QKAKSNPNR) a result of a cross-reactivity triggered by the antigenic region at residues 9-17 of HCV core (RKTKRNTNR)? We c ompared the relative antibody avidity between antibodies reactive to b oth regions, and determined the residues essential for antibody bindin g using substitution peptide analogues. Of 96 sera assayed, 60 were fo und positive for anti-HCV, and of these 55 were found to react with HC V core. Twenty-nine sera were found reactive to the GOR peptide, and t hese were all reactive to HCV core. In most cases the relative antibod y avidity of antibodies reactive to GOR was higher for the HCV core pe ptide. In 21 of the GOR-reactive sera we were able to determine the es sential residues for antibody binding. The essential residues in > 50% of all tested sera coincided with the well conserved residues Lys(10) , Lys(12) Asn(14), and Asn(16). Also, reactivity to GOR was not relate d to any certain serotype of antibodies to HCV. Taken together, these findings explain at the molecular level the observed cross-reactivity between these two proteins, since sequence homology per se is not evid ence for cross-reactivity.