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 : 001C65 ( Istex/Corpus ); précédent : 001C64; suivant : 001C66Genetic 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 ; P. Parroche ; L. Chatel ; C. Barretto ; A. Beck ; C. Trépo ; C. Bain ; Y. C. Lone ; G. Inchauspé ; Anne FournillierSource :
- 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
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ISTEX:AC2E85ADB7D5AB0E593454568B519DFB86D37E92Le document en format XML
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Martin</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Parroche, P" sort="Parroche, P" uniqKey="Parroche P" first="P." last="Parroche">P. Parroche</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Chatel, L" sort="Chatel, L" uniqKey="Chatel L" first="L." last="Chatel">L. Chatel</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Barretto, C" sort="Barretto, C" uniqKey="Barretto C" first="C." last="Barretto">C. Barretto</name><affiliation><mods:affiliation>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</mods:affiliation></affiliation></author><author><name sortKey="Beck, A" sort="Beck, A" uniqKey="Beck A" first="A." last="Beck">A. Beck</name><affiliation><mods:affiliation>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</mods:affiliation></affiliation></author><author><name sortKey="Trepo, C" sort="Trepo, C" uniqKey="Trepo C" first="C." last="Trépo">C. Trépo</name><affiliation><mods:affiliation>Service d'Hépatologie, Hôpital de l'Hôtel‐Dieu, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Bain, C" sort="Bain, C" uniqKey="Bain C" first="C." last="Bain">C. Bain</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Lone, Y C" sort="Lone, Y C" uniqKey="Lone Y" first="Y. C." last="Lone">Y. C. Lone</name><affiliation><mods:affiliation>Institut Pasteur, Unité d'Immunité Cellulaire Antivirale, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Inchauspe, G" sort="Inchauspe, G" uniqKey="Inchauspe G" first="G." last="Inchauspé">G. Inchauspé</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation></author><author><name sortKey="Fournillier, Anne" sort="Fournillier, Anne" uniqKey="Fournillier A" first="Anne" last="Fournillier">Anne Fournillier</name><affiliation><mods:affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: Anne.Fournillier@ens‐lyon.fr</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: FRE 2736, CNRS/ bioMérieux, 46 Allée d'Italie, 69364 Lyon cedex 07, France.===</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Medical Virology</title><title level="j" type="alt">JOURNAL OF MEDICAL VIROLOGY</title><idno type="ISSN">0146-6615</idno><idno type="eISSN">1096-9071</idno><imprint><biblScope unit="vol">74</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="397">397</biblScope><biblScope unit="page" to="405">405</biblScope><biblScope unit="page-count">9</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2004-11">2004-11</date></imprint><idno type="ISSN">0146-6615</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0146-6615</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. 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Martin</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string></affiliations></json:item><json:item><name>P. Parroche</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string></affiliations></json:item><json:item><name>L. Chatel</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string></affiliations></json:item><json:item><name>C. Barretto</name><affiliations><json:string>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</json:string></affiliations></json:item><json:item><name>A. Beck</name><affiliations><json:string>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</json:string></affiliations></json:item><json:item><name>C. Trépo</name><affiliations><json:string>Service d'Hépatologie, Hôpital de l'Hôtel‐Dieu, Lyon, France</json:string></affiliations></json:item><json:item><name>C. Bain</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string></affiliations></json:item><json:item><name>Y.C. Lone</name><affiliations><json:string>Institut Pasteur, Unité d'Immunité Cellulaire Antivirale, Paris, France</json:string></affiliations></json:item><json:item><name>G. Inchauspé</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string></affiliations></json:item><json:item><name>Anne Fournillier</name><affiliations><json:string>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</json:string><json:string>E-mail: Anne.Fournillier@ens‐lyon.fr</json:string><json:string>Correspondence address: FRE 2736, CNRS/ bioMérieux, 46 Allée d'Italie, 69364 Lyon cedex 07, France.===</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>HCV</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>T epitopes</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>immune response</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>cytotoxic T lymphocytes</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IFNγ production</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PBMC</value></json:item></subject><articleId><json:string>JMV20189</json:string></articleId><arkIstex>ark:/67375/WNG-SNSJ6M2F-0</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><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.</abstract><qualityIndicators><score>9.88</score><pdfWordCount>5739</pdfWordCount><pdfCharCount>36102</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>594 x 792 pts</pdfPageSize><pdfWordsPerPage>638</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>240</abstractWordCount><abstractCharCount>1577</abstractCharCount><keywordCount>6</keywordCount></qualityIndicators><title>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</title><pmid><json:string>15368525</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Medical Virology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1096-9071</json:string></doi><issn><json:string>0146-6615</json:string></issn><eissn><json:string>1096-9071</json:string></eissn><publisherId><json:string>JMV</json:string></publisherId><volume>74</volume><issue>3</issue><pages><first>397</first><last>405</last><total>9</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Research Article</value></json:item></subject></host><namedEntities><unitex><date><json:string>2004</json:string></date><geogName></geogName><orgName><json:string>Clonestar</json:string><json:string>Chiron Corp.</json:string><json:string>LISS, INC</json:string><json:string>PeproTech, Inc., London, England</json:string><json:string>Wiley-Liss, Inc</json:string><json:string>Foundation Merieux</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Y.C. Lone</json:string><json:string>Pierre Fabre</json:string><json:string>P. Parroche</json:string><json:string>J. Med</json:string><json:string>I. Panel</json:string><json:string>L. Geburher</json:string><json:string>Anne Fournillier</json:string><json:string>A. Beck</json:string><json:string>Published</json:string></persName><placeName><json:string>Dusseldorf</json:string><json:string>Paris</json:string><json:string>Bristol</json:string><json:string>Germany</json:string><json:string>Emeryville</json:string><json:string>UK</json:string><json:string>Saint Quentin</json:string><json:string>CA</json:string><json:string>France</json:string><json:string>Lyon</json:string><json:string>Belgium</json:string></placeName><ref_url><json:string>http://hepatitis.ibcp.fr</json:string></ref_url><ref_bibl><json:string>Thimme et al., 2001</json:string><json:string>Prezzi et al. 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HCV</title><author xml:id="author-0000"><persName><forename type="first">P.</forename><surname>Martin</surname></persName><affiliation><address><addrLine>FRE 2736 CNRS / bioMérieux</addrLine><addrLine>IFR 128 BioSciences Lyon‐Gerland, Lyon, France</addrLine><country key="FR" xml:lang="en">FRANCE</country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">P.</forename><surname>Parroche</surname></persName><affiliation><address><addrLine>FRE 2736 CNRS / bioMérieux</addrLine><addrLine>IFR 128 BioSciences Lyon‐Gerland, Lyon, France</addrLine><country key="FR" xml:lang="en">FRANCE</country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">L.</forename><surname>Chatel</surname></persName><affiliation><address><addrLine>FRE 2736 CNRS / bioMérieux</addrLine><addrLine>IFR 128 BioSciences Lyon‐Gerland, Lyon, France</addrLine><country key="FR" 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Virol. 74:397–405, 2004. © 2004 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>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</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Identification of Novel Class I Epitopes of HCV</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>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</title></titleInfo><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Martin</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Parroche</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Chatel</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Barretto</namePart><affiliation>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Beck</namePart><affiliation>Centre d'Immunologie Pierre Fabre (CIPF), Saint‐Julien en Genevois, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Trépo</namePart><affiliation>Service d'Hépatologie, Hôpital de l'Hôtel‐Dieu, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Bain</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Y.C.</namePart><namePart type="family">Lone</namePart><affiliation>Institut Pasteur, Unité d'Immunité Cellulaire Antivirale, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Inchauspé</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne</namePart><namePart type="family">Fournillier</namePart><affiliation>FRE 2736 CNRS / bioMérieux, IFR 128 BioSciences Lyon‐Gerland, Lyon, France</affiliation><affiliation>E-mail: Anne.Fournillier@ens‐lyon.fr</affiliation><affiliation>Correspondence address: FRE 2736, CNRS/ bioMérieux, 46 Allée d'Italie, 69364 Lyon cedex 07, France.===</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2004-11</dateIssued><dateValid encoding="w3cdtf">2004-06-21</dateValid><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">2</extent><extent unit="references">40</extent><extent unit="words">1470</extent></physicalDescription><abstract lang="en">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.</abstract><note type="funding">bio Mérieux</note><note type="funding">European Community - No. QLRT‐PL 1999‐00356; No. 2001‐01329; </note><subject lang="en"><genre>keywords</genre><topic>HCV</topic><topic>T epitopes</topic><topic>immune response</topic><topic>cytotoxic T lymphocytes</topic><topic>IFNγ production</topic><topic>PBMC</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Virology</title></titleInfo><titleInfo type="abbreviated"><title>J. Med. 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|texte= 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
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