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HCV core immunodominant region analysis using mouse monoclonal antibodies and human sera: Characterization of major epitopes useful for antigen detection
Author(s) -
JolivetReynaud Colette,
Dalbon Pascal,
Viola Florence,
Yvon Stéphane,
ParanhosBaccala Glauricia,
Piga Nadia,
Bridon Laurence,
Trabaud Mary Anne,
Battail Nicole,
Sibai Geneviève,
Jolivet Michel
Publication year - 1998
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199812)56:4<300::aid-jmv3>3.0.co;2-8
Subject(s) - epitope , monoclonal antibody , virology , antigen , epitope mapping , conformational epitope , antibody , linear epitope , biology , recombinant dna , microbiology and biotechnology , hepatitis c virus , virus , chemistry , biochemistry , immunology , gene
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, 29–33). 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, and GRTWAQPGYPWPLY (residues 7–17, 34–39, and 73–86, 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. J. Med. Virol. 56:300–309, 1998 . © 1998 Wiley‐Liss, Inc.