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
Identifieur interne : 000219 ( France/Analysis ); précédent : 000218; suivant : 000220Genetic immunization and comprehensive screening approaches in HLA‐A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen
Auteurs : P. Martin [France] ; P. Parroche [France] ; L. Chatel [France] ; C. Barretto [France] ; A. Beck [France] ; C. Trépo [France] ; C. Bain [France] ; Y. C. Lone [France] ; G. Inchauspé [France] ; Anne Fournillier [France]Source :
- Journal of Medical Virology [ 0146-6615 ] ; 2004-11.
Abstract
Interferon‐γ (IFNγ)‐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 IFNγ‐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 IFNγ and IL‐10‐producing T cells from peripheral blood mononuclear cells (PBMC) of chronically infected patients. These data increase the pool of NS3‐specific CD8+ T cell epitopes available to analyze HCV associated immunity and could contribute to the design and evaluation of candidate vaccines. J. Med. Virol. 74:397–405, 2004. © 2004 Wiley‐Liss, Inc.
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DOI: 10.1002/jmv.20189
Affiliations:
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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 IFNγ‐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 IFNγ and IL‐10‐producing T cells from peripheral blood mononuclear cells (PBMC) of chronically infected patients. These data increase the pool of NS3‐specific CD8+ T cell epitopes available to analyze HCV associated immunity and could contribute to the design and evaluation of candidate vaccines. J. Med. Virol. 74:397–405, 2004. © 2004 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li><li>Île-de-France</li></region><settlement><li>Lyon</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Martin, P" sort="Martin, P" uniqKey="Martin P" first="P." last="Martin">P. Martin</name></region><name sortKey="Bain, C" sort="Bain, C" uniqKey="Bain C" first="C." last="Bain">C. Bain</name><name sortKey="Barretto, C" sort="Barretto, C" uniqKey="Barretto C" first="C." last="Barretto">C. Barretto</name><name sortKey="Beck, A" sort="Beck, A" uniqKey="Beck A" first="A." last="Beck">A. Beck</name><name sortKey="Chatel, L" sort="Chatel, L" uniqKey="Chatel L" first="L." last="Chatel">L. Chatel</name><name sortKey="Fournillier, Anne" sort="Fournillier, Anne" uniqKey="Fournillier A" first="Anne" last="Fournillier">Anne Fournillier</name><name sortKey="Fournillier, Anne" sort="Fournillier, Anne" uniqKey="Fournillier A" first="Anne" last="Fournillier">Anne Fournillier</name><name sortKey="Fournillier, Anne" sort="Fournillier, Anne" uniqKey="Fournillier A" first="Anne" last="Fournillier">Anne Fournillier</name><name sortKey="Inchauspe, G" sort="Inchauspe, G" uniqKey="Inchauspe G" first="G." last="Inchauspé">G. Inchauspé</name><name sortKey="Lone, Y C" sort="Lone, Y C" uniqKey="Lone Y" first="Y. C." last="Lone">Y. C. Lone</name><name sortKey="Parroche, P" sort="Parroche, P" uniqKey="Parroche P" first="P." last="Parroche">P. Parroche</name><name sortKey="Trepo, C" sort="Trepo, C" uniqKey="Trepo C" first="C." last="Trépo">C. Trépo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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