Mapping of antigenic determinants of hepatitis C virus proteins using phage display |
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Authors: | E. A. Rechkina G. F. Denisova O. V. Masalova L. F. Lideman D. A. Denisov E. I. Lesnova R. I. Ataullakhanov S. V. Gurianova A. A. Kushch |
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Affiliation: | (1) Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscow, 123098, Russia;(2) Department of Cell Research and Immunology, Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel;(3) Immapharma Joint-Stock Company, Moscow, 123098, Russia;(4) Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia |
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Abstract: | Analysis of the properties for individual hepatitis C virus (HCV) proteins makes it possible to establish their molecular structure and conformation, to localize antigenic and immunogenic determinants, to identify protective epitopes, and to solve applied problems (e.g., design of diagnostic tests, vaccines, and drugs). Linear and conformational epitopes of HCV proteins were localized using the phage display technique, and the peptides exposed on the phages selected with monoclonal antibodies against HCV proteins were tested for immunogenicity. Of the 11 epitopes revealed, three were strongly linear; two depended on the secondary; and one on the tertiary structure of the corresponding protein (conformational epitopes). Amino acid sequences involved in the other epitopes were established. The results can be used to improve the diagnosis of hepatitis C, to study the effect of amino acid substitutions on the antigenic properties of HCV proteins, and to analyze the immune response in patients infected with genotypically different HCV. It was shown with the example of the NS5A epitope that phage particles with epitope-mimicking peptides (mimotopes) induce production of antibodies against the corresponding HCV proteins. |
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Keywords: | hepatitis C virus proteins antigenic determinants epitope mapping phage display immunogenic properties |
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