ISOTYPE-SPECIFIC IMMUNE-RESPONSE TO A SINGLE HEPATITIS-C VIRUS CORE EPITOPE DEFINED BY A HUMAN MONOCLONAL-ANTIBODY - DIAGNOSTIC-VALUE AND CORRELATION TO PCR

In this study we tested the seroreactivity of 223 selected anti-HCV-re active blood donors to the human B-cell epitope N-VYLLPR-C (C-34-39) O f the hepatitis C virus core antigen. The epitope was recently identif ied and characterized by the human monoclonal IgG antibody U1/F10 [23] and is located within the amino acid residues 34-39 of the aminotermi nal core region. The blood donor sera were selected from anti-HCV ELIS A (Ortho, 2nd generation)-reactive samples. Sixty-seven of these sera were further reactive in RIBA (Ortho, 2nd generation). According to th eir RIBA pattern, these samples were divided into four groups. Samples in the first group (n = 18) reacted to all four recombinant HCV antig ens. The samples of the second (n = 9) and third group (n = 8) reacted to c22-3/c33c and c22-3/c100-3, respectively. Sera from group 4 (n = 32) showed a RIBA indeterminate pattern with reactivity only to c22-3. All 223 samples were analyzed for anti-C-34-39 antibodies by ELISA, a nd the 67 RIBA-reactive samples were additionally tested for the prese nce of HCV RNA by RT/PCR. In groups 1 and 2, over 80% of the samples s howed anti-C-34-39 reactivity which was restricted to the IgG(1) isoty pe. In contrast, in groups 3 and 4, antibodies to the epitope C-34-39 were detected in less than 10% of the samples. Interestingly, the anti -C-34-39 response correlates with the presence of HCV RNA; 95.5% of th e samples had coincident results in all subgroups. None of the RIBA-ne gative sera showed a specific seroreaction to the C-34-39 peptide.