HCV core immunodominant region analysis using mouse monoclonal antibodies and human sera: Characterization of major epitopes useful for antigen detection
✍ Scribed by Jolivet-Reynaud, Colette; Dalbon, Pascal; Viola, Florence; Yvon, Stéphane; Paranhos-Baccala, Glauricia; Piga, Nadia; Bridon, Laurence; Trabaud, Mary Anne; Battail, Nicole; Sibai, Geneviève; Jolivet, Michel
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 143 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Monoclonal antibodies (MAbs) were generated by immunizing mice with a truncated recombinant protein corresponding to the immunodominant region (residues 1-120) of hepatitis C virus (HCV) nucleocapsid protein. The specific recognition by either human sera or mouse monoclonal antibodies of overlapping peptides spanning the core region 1-120 as well as the comparison with epitopes described earlier allowed the fine mapping of HCV core. Within the region 1-120, the major antigenic domain could be restricted to the first 45 amino acids. Indeed, the peptide S42G (residues 2-45) allowed the detection of an anti-HCV core response by all anticore-positive human sera examined. According to their epitope localization, three groups of mouse MABs could be evidenced that were directed against different regions of core. Group II MAbs recognized a strictly linear epitope (QDVKF, residues 20-24), whereas group I MABs were directed against a conformational epitope mainly located at the amino acid residues (QIVGG,(29)(30)(31)(32)(33). The epitope of group III MABs was also conformational (PRGRRQPI, residues 58-65). These three epitopes appeared close but different from the three major human epitopes RKTKRNTN, VYLLPR,[34][35][36][37][38][39][73][74][75][76][77][78][79][80][81][82][83][84][85][86] respectively). Group II MAB 7G12A8 and group I MAB 19D9D6 were used in a sandwich ELISA for the capture and the detection, respectively, of viral core antigen in sera of patients with chronic HCV infection. After treatment of sera with triton × 100 in acidic conditions, amounts of viral antigen as low as 20 pg/ml of sera could be detected.