Genetic immunization and comprehensive screening approaches in HLA-A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen

Journal of Medical Virology
P MartinA Fournillier

Abstract

Interferon-gamma (IFN gamma)-producing CD8+ T cells have been shown to play a key role in the control or eradication of hepatitis C virus (HCV) infections. In particular, T cells specific of the non-structural protein 3 (NS3) are often associated with control of viremia. The aim of the study was to identify novel HLA-A2 restricted CD8+ T cell epitopes specific of NS3 using a combination of comprehensive approaches. HLA-A2.1 transgenic mice were immunized with a DNA vaccine optimized for NS3 specific epitope presentation and induced CD8+ T cell reactivity was screened using 42 algorithm-predicted peptides as well as a library of 78 overlapping 15-mer peptides spanning the whole protein. Three epitopes mapping within the NS3 protease (GLL: aa 1038-1047) or helicase (ATL: aa 1260-1268 and TLH: aa 1617-1625) were identified. These epitopes, which display similar and high in vitro binding capacities to soluble HLA-A2 molecules, are able to induce either cytotoxic T lymphocytes (CTL) and/or IFN gamma-producing T cells. Comparative in vitro target cell sensitization studies revealed a higher immunogenicity of the GLL peptide as compared with both ATL and TLH peptides. This peptide was capable to recall in vitro HCV-specific IFN gamma ...Continue Reading

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Citations

Oct 10, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aintzane ZabaletaPablo Sarobe
Jul 16, 2005·Expert Opinion on Biological Therapy·Steve Pascolo
Jul 3, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Alain BeckNathalie Corvaïa
Jul 20, 2005·Expert Review of Vaccines·Geert Leroux-Roels
Jan 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marianne MikkelsenJan Pravsgaard Christensen
Feb 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer N UramElizabeth M Jaffee

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