Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81
| Autor: | Katarina Drakenberg, Michael Houghton, Lena Grillner, Mats A. A. Persson, Domenico Rosa, Aster Beyene, Sergio Abrignani, Anders Widell, Tobias Allander |
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| Rok vydání: | 2000 |
| Předmět: |
Genotype
medicine.drug_class Protein Conformation Molecular Sequence Data Quantitative Structure-Activity Relationship CHO Cells Hepacivirus Monoclonal antibody Epitope Immunoglobulin G law.invention Tetraspanin 28 Immunoglobulin Fab Fragments Antigen Viral Envelope Proteins law Antigens CD Bone Marrow Virology Cricetinae medicine Animals Humans Amino Acid Sequence biology Antibodies Monoclonal Membrane Proteins Hepatitis C Antibodies Molecular biology Recombinant Proteins Tissue Donors Epitope mapping biology.protein Recombinant DNA Antibody Epitope Mapping |
| Zdroj: | The Journal of general virology. 81(Pt 10) |
| ISSN: | 0022-1317 |
| Popis: | The antibody response to the envelope proteins of hepatitis C virus (HCV) may play an important role in controlling the infection. To allow molecular analyses of protective antibodies, we isolated human monoclonal antibodies to the E2 envelope glycoprotein of HCV from a combinatorial Fab library established from bone marrow of a chronically HCV-infected patient. Anti-E2 reactive clones were selected using recombinant E2 protein. The bone marrow donor carried HCV genotype 2b, and E2 used for selection was of genotype 1a. The antibody clones were expressed as Fab fragments in E. coli, and as Fab fragments and IgG1 in CHO cells. Seven different antibody clones were characterized, and shown to have high affinity for E2, genotype 1a. Three clones also had high affinity for E2 of genotype 1b. They all bind to conformation-dependent epitopes. Five clones compete for the same or overlapping binding sites, while two bind to one or two other epitopes of E2. Four clones corresponding to the different epitopes were tested as purified IgG1 for blocking the CD81–E2 interaction in vitro; all four were positive at 0·3–0·5 μg/ml. Thus, the present results suggest the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2–CD81 interaction, of which one appeared immunodominant in this donor. |
| Databáze: | OpenAIRE |
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