Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization
Identifieur interne : 001768 ( Istex/Corpus ); précédent : 001767; suivant : 001769Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization
Auteurs : Alexander Y. Lee ; Noelle K. Polakos ; Gillis R. Otten ; Jeffrey B. Ulmer ; Michael Houghton ; Xavier PaliardSource :
- Vaccine [ 0264-410X ] ; 2000.
English descriptors
- Teeft :
- Acute hepatitis, Assay, Cell epitopes, Cell repertoire, Cytometry, Cytotoxic, Cytotoxic activity, Days post booster, Elsevier science, Epitope, Gene expression, Hepatitis, Immune, Immune response, Immune responses, Immunization, Important role, Individual mice, Individual peptides, Intracellular, Intracellular staining, Mouse, Natural history, Ns5a, Ns5b, Peptide, Peptide pool, Plasmid, Release assay, Restimulated, Restimulation, Spleen, Spleen cells, Svbalb target cells, Target cells, Unpublished observations, Vaccine, Vaccine strategies, Viral, Viral infection, Virol shirai, Virus infection.
Abstract
Abstract: Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.
Url:
DOI: 10.1016/S0264-410X(99)00486-7
Links to Exploration step
ISTEX:DCB983433EEA259DB4AD272A73DDFDDF088E1B83Le document en format XML
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Ulmer</name><affiliation><mods:affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</mods:affiliation></affiliation></author><author><name sortKey="Houghton, Michael" sort="Houghton, Michael" uniqKey="Houghton M" first="Michael" last="Houghton">Michael Houghton</name><affiliation><mods:affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</mods:affiliation></affiliation></author><author><name sortKey="Paliard, Xavier" sort="Paliard, Xavier" uniqKey="Paliard X" first="Xavier" last="Paliard">Xavier Paliard</name><affiliation><mods:affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: xavier_paliard@cc.chiron.com</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Vaccine</title><title level="j" type="abbrev">JVAC</title><idno type="ISSN">0264-410X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="1962">1962</biblScope><biblScope unit="page" to="1968">1968</biblScope></imprint><idno type="ISSN">0264-410X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acute hepatitis</term><term>Assay</term><term>Cell epitopes</term><term>Cell repertoire</term><term>Cytometry</term><term>Cytotoxic</term><term>Cytotoxic activity</term><term>Days post booster</term><term>Elsevier science</term><term>Epitope</term><term>Gene expression</term><term>Hepatitis</term><term>Immune</term><term>Immune response</term><term>Immune responses</term><term>Immunization</term><term>Important role</term><term>Individual mice</term><term>Individual peptides</term><term>Intracellular</term><term>Intracellular staining</term><term>Mouse</term><term>Natural history</term><term>Ns5a</term><term>Ns5b</term><term>Peptide</term><term>Peptide pool</term><term>Plasmid</term><term>Release assay</term><term>Restimulated</term><term>Restimulation</term><term>Spleen</term><term>Spleen cells</term><term>Svbalb target cells</term><term>Target cells</term><term>Unpublished observations</term><term>Vaccine</term><term>Vaccine strategies</term><term>Viral</term><term>Viral infection</term><term>Virol shirai</term><term>Virus infection</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>epitope</json:string><json:string>peptide</json:string><json:string>cytotoxic</json:string><json:string>spleen cells</json:string><json:string>intracellular</json:string><json:string>ns5a</json:string><json:string>cytometry</json:string><json:string>vaccine</json:string><json:string>plasmid</json:string><json:string>restimulated</json:string><json:string>release assay</json:string><json:string>ns5b</json:string><json:string>viral</json:string><json:string>restimulation</json:string><json:string>immune</json:string><json:string>target cells</json:string><json:string>assay</json:string><json:string>immunization</json:string><json:string>intracellular staining</json:string><json:string>individual mice</json:string><json:string>immune responses</json:string><json:string>cell repertoire</json:string><json:string>hepatitis</json:string><json:string>spleen</json:string><json:string>unpublished observations</json:string><json:string>virus infection</json:string><json:string>vaccine strategies</json:string><json:string>cytotoxic activity</json:string><json:string>viral infection</json:string><json:string>peptide pool</json:string><json:string>acute hepatitis</json:string><json:string>mouse</json:string><json:string>elsevier science</json:string><json:string>important role</json:string><json:string>virol shirai</json:string><json:string>svbalb target cells</json:string><json:string>days post booster</json:string><json:string>natural history</json:string><json:string>cell epitopes</json:string><json:string>individual peptides</json:string><json:string>immune response</json:string><json:string>gene expression</json:string></teeft></keywords><author><json:item><name>Alexander Y. Lee</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string></affiliations></json:item><json:item><name>Noelle K. Polakos</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string></affiliations></json:item><json:item><name>Gillis R. Otten</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string></affiliations></json:item><json:item><name>Jeffrey B. Ulmer</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string></affiliations></json:item><json:item><name>Michael Houghton</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string></affiliations></json:item><json:item><name>Xavier Paliard</name><affiliations><json:string>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</json:string><json:string>E-mail: xavier_paliard@cc.chiron.com</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>DNA immunization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HCV</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CTL</value></json:item></subject><arkIstex>ark:/67375/6H6-MLBQH8BG-W</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.</abstract><qualityIndicators><score>7.208</score><pdfWordCount>3480</pdfWordCount><pdfCharCount>21512</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>595 x 842 pts (A4)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>144</abstractWordCount><abstractCharCount>958</abstractCharCount><keywordCount>3</keywordCount></qualityIndicators><title>Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</title><pmid><json:string>10699347</json:string></pmid><pii><json:string>S0264-410X(99)00486-7</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Vaccine</title><language><json:string>unknown</json:string></language><publicationDate>2000</publicationDate><issn><json:string>0264-410X</json:string></issn><pii><json:string>S0264-410X(00)X0100-4</json:string></pii><volume>18</volume><issue>18</issue><pages><first>1962</first><last>1968</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2000</json:string><json:string>4276</json:string><json:string>15-5-5</json:string></date><geogName></geogName><orgName><json:string>Jackson Laboratories</json:string><json:string>Research Genetics</json:string><json:string>Elsevier Science Ltd.</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>D. Atchley</json:string><json:string>Xavier Paliard</json:string><json:string>K. Polakos</json:string><json:string>X. Paliard</json:string><json:string>Michael Houghton</json:string><json:string>B. Ulmer</json:string><json:string>M. Selby</json:string><json:string>N. Cronen</json:string><json:string>R. Otten</json:string><json:string>A. Lee</json:string><json:string>P. Benitez</json:string></persName><placeName><json:string>San Diego</json:string><json:string>Australia</json:string><json:string>CA</json:string><json:string>AL</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[23]</json:string><json:string>[18]</json:string><json:string>Chiron Corporation, 4560</json:string><json:string>[22]</json:string><json:string>[21]</json:string><json:string>[20]</json:string><json:string>[5]</json:string><json:string>[19,20]</json:string><json:string>[13]</json:string><json:string>A.Y. Lee et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-MLBQH8BG-W</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - medicine, research & experimental</json:string><json:string>2 - immunology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - virology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Public Health, Environmental and Occupational Health</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Veterinary</json:string><json:string>3 - General Veterinary</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - General Immunology and Microbiology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Molecular Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - sarcoidoses. granulomatoses d'etiologie indeterminee. maladies du tissu conjonctif. maladies du tissu elastique. vascularites</json:string></inist></categories><publicationDate>2000</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1016/S0264-410X(99)00486-7</json:string></doi><id>DCB983433EEA259DB4AD272A73DDFDDF088E1B83</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-MLBQH8BG-W/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-MLBQH8BG-W/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-MLBQH8BG-W/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a">Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©2000 Elsevier Science Ltd</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>2000</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Fig. 1: Mapping of HCV-NS5a regions recognized by CD8+ T cells. Spleen cells from DNA immunized, VV boosted C3H/HeJ mice were cultured in media alone or restimulated ex vivo with peptide pools (4–6 peptides per pool) or individual peptides and stained for surface CD8 and intracellular IFN-γ with anti-CD8-FITC and anti-IFN-γ-PE, respectively. Lymphocytes were first gated by side vs forward scatter light and then for CD8-FITC. Plots show log fluorescence intensity for CD8 (FITC) and IFN-γ (PE) observed for a representative individual mouse.</note><note type="content">Fig. 2: P214K9-specific CD8+ T cells are cytotoxic. Spleen cells from DNA-NS5a immunized C3H/HeJ (H-2k) mice were pooled and restimulated in vitro with p214. Cultures were then tested for cytotoxic activity in a standard 51Cr release assay against L929 (H-2k) target cells sensitized with (■) p214, (▾) p214 K, (⋅) p214K9, (×) p214J, or, SvBalb (H-2d) target cells sensitized with (□) p214 or (○) p214K9.</note><note type="content">Table 1: Summary of HCV-specific CTL epitope mapping in various mouse strains by flow cytometry</note><note type="content">Table 2: p214K9-specific CTL in C3H/HeJ mice primed with DNA-NS5a and boosted with either DNA-NS5a or VV-NS5a</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</title><author xml:id="author-0000"><persName><forename type="first">Alexander Y.</forename><surname>Lee</surname></persName><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Noelle K.</forename><surname>Polakos</surname></persName><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Gillis R.</forename><surname>Otten</surname></persName><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Jeffrey B.</forename><surname>Ulmer</surname></persName><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Michael</forename><surname>Houghton</surname></persName><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Xavier</forename><surname>Paliard</surname></persName><email>xavier_paliard@cc.chiron.com</email><note type="correspondence"><p>Corresponding author. Tel.: +1-510-923-3545; fax: +1-510-923-2586</p></note><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation></author><idno type="istex">DCB983433EEA259DB4AD272A73DDFDDF088E1B83</idno><idno type="ark">ark:/67375/6H6-MLBQH8BG-W</idno><idno type="DOI">10.1016/S0264-410X(99)00486-7</idno><idno type="PII">S0264-410X(99)00486-7</idno></analytic><monogr><title level="j">Vaccine</title><title level="j" type="abbrev">JVAC</title><idno type="pISSN">0264-410X</idno><idno type="PII">S0264-410X(00)X0100-4</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">18</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="1962">1962</biblScope><biblScope unit="page" to="1968">1968</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>DNA immunization</term></item><item><term>HCV</term></item><item><term>CTL</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999-10-15">Modified</change><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-MLBQH8BG-W/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>JVAC</jid><aid>1924</aid><ce:pii>S0264-410X(99)00486-7</ce:pii><ce:doi>10.1016/S0264-410X(99)00486-7</ce:doi><ce:copyright type="full-transfer" year="2000">Elsevier Science Ltd</ce:copyright></item-info><head><ce:title>Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</ce:title><ce:author-group><ce:author><ce:given-name>Alexander Y.</ce:given-name><ce:surname>Lee</ce:surname></ce:author><ce:author><ce:given-name>Noelle K.</ce:given-name><ce:surname>Polakos</ce:surname></ce:author><ce:author><ce:given-name>Gillis R.</ce:given-name><ce:surname>Otten</ce:surname></ce:author><ce:author><ce:given-name>Jeffrey B.</ce:given-name><ce:surname>Ulmer</ce:surname></ce:author><ce:author><ce:given-name>Michael</ce:given-name><ce:surname>Houghton</ce:surname></ce:author><ce:author><ce:given-name>Xavier</ce:given-name><ce:surname>Paliard</ce:surname><ce:cross-ref refid="COR1">*</ce:cross-ref><ce:e-address>xavier_paliard@cc.chiron.com</ce:e-address></ce:author><ce:affiliation><ce:textfn>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +1-510-923-3545; fax: +1-510-923-2586</ce:text></ce:correspondence></ce:author-group><ce:date-received day="19" month="7" year="1999"></ce:date-received><ce:date-revised day="15" month="10" year="1999"></ce:date-revised><ce:date-accepted day="15" month="10" year="1999"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>DNA immunization</ce:text></ce:keyword><ce:keyword><ce:text>HCV</ce:text></ce:keyword><ce:keyword><ce:text>CTL</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Quantification of the number of cytotoxic T cells specific for an immunodominant HCV-specific CTL epitope primed by DNA immunization</title></titleInfo><name type="personal"><namePart type="given">Alexander Y.</namePart><namePart type="family">Lee</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Noelle K.</namePart><namePart type="family">Polakos</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gillis R.</namePart><namePart type="family">Otten</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeffrey B.</namePart><namePart type="family">Ulmer</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Houghton</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xavier</namePart><namePart type="family">Paliard</namePart><affiliation>Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA</affiliation><affiliation>E-mail: xavier_paliard@cc.chiron.com</affiliation><description>Corresponding author. Tel.: +1-510-923-3545; fax: +1-510-923-2586</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><dateModified encoding="w3cdtf">1999-10-15</dateModified><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Priming of strong cellular immune responses to hepatitis C (HCV) is thought to be important for eradication of infection. Although productive infection of HCV occurs only reproducibly in humans and chimpanzees, definition of HCV-specific T cell epitopes in mice is necessary to screen efficiently HCV vaccine strategies for their ability to prime cellular immune responses. Out of seven strains of mice screened for immunodominant CTL epitopes against HCV-1a Core, E2, NS5a and NS5b, only one epitope (p214K9) in only one mouse strain was identified. Enumeration of p214K9-specific CD8+ cells by flow cytometry revealed that the number of epitope specific CTL primed by ‘naked’ DNA immunization was lower than that reported during viral infection. The p214K9 epitope described here, combined with analysis of CTL responses by flow cytometry, should be instrumental in ranking various HCV vaccine strategies for their ability to prime CTL responses.</abstract><note type="content">Fig. 1: Mapping of HCV-NS5a regions recognized by CD8+ T cells. Spleen cells from DNA immunized, VV boosted C3H/HeJ mice were cultured in media alone or restimulated ex vivo with peptide pools (4–6 peptides per pool) or individual peptides and stained for surface CD8 and intracellular IFN-γ with anti-CD8-FITC and anti-IFN-γ-PE, respectively. Lymphocytes were first gated by side vs forward scatter light and then for CD8-FITC. Plots show log fluorescence intensity for CD8 (FITC) and IFN-γ (PE) observed for a representative individual mouse.</note><note type="content">Fig. 2: P214K9-specific CD8+ T cells are cytotoxic. Spleen cells from DNA-NS5a immunized C3H/HeJ (H-2k) mice were pooled and restimulated in vitro with p214. Cultures were then tested for cytotoxic activity in a standard 51Cr release assay against L929 (H-2k) target cells sensitized with (■) p214, (▾) p214 K, (⋅) p214K9, (×) p214J, or, SvBalb (H-2d) target cells sensitized with (□) p214 or (○) p214K9.</note><note type="content">Table 1: Summary of HCV-specific CTL epitope mapping in various mouse strains by flow cytometry</note><note type="content">Table 2: p214K9-specific CTL in C3H/HeJ mice primed with DNA-NS5a and boosted with either DNA-NS5a or VV-NS5a</note><subject><genre>Keywords</genre><topic>DNA immunization</topic><topic>HCV</topic><topic>CTL</topic></subject><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><titleInfo type="abbreviated"><title>JVAC</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued></originInfo><identifier type="ISSN">0264-410X</identifier><identifier type="PII">S0264-410X(00)X0100-4</identifier><part><date>2000</date><detail type="volume"><number>18</number><caption>vol.</caption></detail><detail type="issue"><number>18</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1873</start><end>1970</end></extent><extent unit="pages"><start>1962</start><end>1968</end></extent></part></relatedItem><identifier type="istex">DCB983433EEA259DB4AD272A73DDFDDF088E1B83</identifier><identifier type="ark">ark:/67375/6H6-MLBQH8BG-W</identifier><identifier type="DOI">10.1016/S0264-410X(99)00486-7</identifier><identifier type="PII">S0264-410X(99)00486-7</identifier><accessCondition type="use and reproduction" contentType="copyright">©2000 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science Ltd, ©2000</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-MLBQH8BG-W/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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