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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations</title><author><name sortKey="Hill, Brenna J" sort="Hill, Brenna J" uniqKey="Hill B" first="Brenna J." last="Hill">Brenna J. Hill</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Darrah, Patricia A" sort="Darrah, Patricia A" uniqKey="Darrah P" first="Patricia A." last="Darrah">Patricia A. Darrah</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Ende, Zachary" sort="Ende, Zachary" uniqKey="Ende Z" first="Zachary" last="Ende">Zachary Ende</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Ambrozak, David R" sort="Ambrozak, David R" uniqKey="Ambrozak D" first="David R." last="Ambrozak">David R. Ambrozak</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Quinn, Kylie M" sort="Quinn, Kylie M" uniqKey="Quinn K" first="Kylie M." last="Quinn">Kylie M. Quinn</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Darko, Sam" sort="Darko, Sam" uniqKey="Darko S" first="Sam" last="Darko">Sam Darko</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name><affiliation><nlm:aff id="aff3">Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Van Den Berg, Hugo A" sort="Van Den Berg, Hugo A" uniqKey="Van Den Berg H" first="Hugo A." last="Van Den Berg">Hugo A. Van Den Berg</name><affiliation><nlm:aff id="aff4">Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Larsen, Martin" sort="Larsen, Martin" uniqKey="Larsen M" first="Martin" last="Larsen">Martin Larsen</name><affiliation><nlm:aff wicri:cut="; and" id="aff6">INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, F-75013 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Centre d’Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Seder, Robert A" sort="Seder, Robert A" uniqKey="Seder R" first="Robert A." last="Seder">Robert A. Seder</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25348625</idno><idno type="pmc">4238745</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238745</idno><idno type="RBID">PMC:4238745</idno><idno type="doi">10.4049/jimmunol.1401017</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001967</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001967</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations</title><author><name sortKey="Hill, Brenna J" sort="Hill, Brenna J" uniqKey="Hill B" first="Brenna J." last="Hill">Brenna J. Hill</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Darrah, Patricia A" sort="Darrah, Patricia A" uniqKey="Darrah P" first="Patricia A." last="Darrah">Patricia A. Darrah</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Ende, Zachary" sort="Ende, Zachary" uniqKey="Ende Z" first="Zachary" last="Ende">Zachary Ende</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Ambrozak, David R" sort="Ambrozak, David R" uniqKey="Ambrozak D" first="David R." last="Ambrozak">David R. Ambrozak</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Quinn, Kylie M" sort="Quinn, Kylie M" uniqKey="Quinn K" first="Kylie M." last="Quinn">Kylie M. Quinn</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Darko, Sam" sort="Darko, Sam" uniqKey="Darko S" first="Sam" last="Darko">Sam Darko</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name><affiliation><nlm:aff id="aff3">Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Van Den Berg, Hugo A" sort="Van Den Berg, Hugo A" uniqKey="Van Den Berg H" first="Hugo A." last="Van Den Berg">Hugo A. Van Den Berg</name><affiliation><nlm:aff id="aff4">Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Larsen, Martin" sort="Larsen, Martin" uniqKey="Larsen M" first="Martin" last="Larsen">Martin Larsen</name><affiliation><nlm:aff wicri:cut="; and" id="aff6">INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, F-75013 Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Centre d’Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France</nlm:aff></affiliation></author><author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Seder, Robert A" sort="Seder, Robert A" uniqKey="Seder R" first="Robert A." last="Seder">Robert A. Seder</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name><affiliation><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Immunology Author Choice</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K<sup>d</sup> epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2D<sup>d</sup> epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2D<sup>d</sup> specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Immunol</journal-id><journal-id journal-id-type="iso-abbrev">J. Immunol</journal-id><journal-id journal-id-type="hwp">jimmunol</journal-id><journal-id journal-id-type="pmc">jimmunol</journal-id><journal-id journal-id-type="publisher-id">JI</journal-id><journal-title-group><journal-title>The Journal of Immunology Author Choice</journal-title></journal-title-group><issn pub-type="ppub">0022-1767</issn><issn pub-type="epub">1550-6606</issn><publisher><publisher-name>AAI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25348625</article-id><article-id pub-id-type="pmc">4238745</article-id><article-id pub-id-type="publisher-id">ji_1401017</article-id><article-id pub-id-type="doi">10.4049/jimmunol.1401017</article-id><article-categories><subj-group subj-group-type="heading"><subject>Infectious Disease and Host Response</subject></subj-group></article-categories><title-group><article-title>Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hill</surname><given-names>Brenna J.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Darrah</surname><given-names>Patricia A.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Ende</surname><given-names>Zachary</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Ambrozak</surname><given-names>David R.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Quinn</surname><given-names>Kylie M.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Darko</surname><given-names>Sam</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Gostick</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Wooldridge</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="aff3">‡</xref></contrib><contrib contrib-type="author"><name><surname>van den Berg</surname><given-names>Hugo A.</given-names></name><xref ref-type="aff" rid="aff4">§</xref></contrib><contrib contrib-type="author"><name><surname>Venturi</surname><given-names>Vanessa</given-names></name><xref ref-type="aff" rid="aff5">¶</xref></contrib><contrib contrib-type="author"><name><surname>Larsen</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="aff6">‖</xref><xref ref-type="aff" rid="aff7">#</xref></contrib><contrib contrib-type="author"><name><surname>Davenport</surname><given-names>Miles P.</given-names></name><xref ref-type="aff" rid="aff5">¶</xref></contrib><contrib contrib-type="author"><name><surname>Seder</surname><given-names>Robert A.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Price</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Douek</surname><given-names>Daniel C.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><aff id="aff1"><label>*</label>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</aff><aff id="aff2"><label>†</label>Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</aff><aff id="aff3"><label>‡</label>Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;</aff><aff id="aff4"><label>§</label>Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;</aff><aff id="aff5"><label>¶</label>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</aff><aff id="aff6"><label>‖</label>INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, F-75013 Paris, France; and</aff><aff id="aff7"><label>#</label>Centre d’Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France</aff></contrib-group><author-notes><corresp id="cor1">Address correspondence and reprint requests to Dr. Daniel C. Douek or Dr. David A. Price, Vaccine Research Center/National Institutes of Health, 40 Convent Drive, Room 3509, Bethesda, MD 20892 (D.C.D.) or Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, U.K. (D.A.P.). E-mail addresses: <email>ddouek@mail.nih.gov</email> (D.C.D.) or <email>priced6@cardiff.ac.uk</email> (D.A.P.)</corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>12</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>27</day><month>10</month><year>2014</year></pub-date><volume>193</volume><issue>11</issue><fpage>5626</fpage><lpage>5636</lpage><history><date date-type="received"><day>18</day><month>4</month><year>2014</year></date><date date-type="accepted"><day>03</day><month>10</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 by The American Association of Immunologists, Inc.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Copyright © 2014 by The American Association of Immunologists, Inc.</copyright-holder><license license-type="open-access"><license-p>This article is distributed under The American Association of Immunologists, Inc., <underline><ext-link ext-link-type="uri" xlink:href="http://www.jimmunol.org/site/misc/authorchoice.xhtml">Reuse Terms and Conditions for Author Choice articles</ext-link></underline>.</license-p></license></permissions><abstract><p>Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K<sup>d</sup> epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2D<sup>d</sup> epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2D<sup>d</sup> specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.</p></abstract><counts><page-count count="11"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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