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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve<xref rid="FN2" ref-type="fn">1</xref></title><author><name sortKey="Oseroff, Carla" sort="Oseroff, Carla" uniqKey="Oseroff C" first="Carla" last="Oseroff">Carla Oseroff</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Peters, Bjoern" sort="Peters, Bjoern" uniqKey="Peters B" first="Bjoern" last="Peters">Bjoern Peters</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Pasquetto, Valerie" sort="Pasquetto, Valerie" uniqKey="Pasquetto V" first="Valerie" last="Pasquetto">Valerie Pasquetto</name></author><author><name sortKey="Moutaftsi, Magdalini" sort="Moutaftsi, Magdalini" uniqKey="Moutaftsi M" first="Magdalini" last="Moutaftsi">Magdalini Moutaftsi</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Sidney, John" sort="Sidney, John" uniqKey="Sidney J" first="John" last="Sidney">John Sidney</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Panchanathan, Vijay" sort="Panchanathan, Vijay" uniqKey="Panchanathan V" first="Vijay" last="Panchanathan">Vijay Panchanathan</name><affiliation><nlm:aff id="A2"> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</nlm:aff></affiliation></author><author><name sortKey="Tscharke, David C" sort="Tscharke, David C" uniqKey="Tscharke D" first="David C." last="Tscharke">David C. Tscharke</name><affiliation><nlm:aff id="A2"> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</nlm:aff></affiliation></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillere">Bernard Maillere</name><affiliation><nlm:aff id="A3"> Institut de Biologie et Technologies de Saclay, Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif sur Yvette, France</nlm:aff></affiliation></author><author><name sortKey="Grey, Howard" sort="Grey, Howard" uniqKey="Grey H" first="Howard" last="Grey">Howard Grey</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18490718</idno><idno type="pmc">2533852</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533852</idno><idno type="RBID">PMC:2533852</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">001449</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001449</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve<xref rid="FN2" ref-type="fn">1</xref></title><author><name sortKey="Oseroff, Carla" sort="Oseroff, Carla" uniqKey="Oseroff C" first="Carla" last="Oseroff">Carla Oseroff</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Peters, Bjoern" sort="Peters, Bjoern" uniqKey="Peters B" first="Bjoern" last="Peters">Bjoern Peters</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Pasquetto, Valerie" sort="Pasquetto, Valerie" uniqKey="Pasquetto V" first="Valerie" last="Pasquetto">Valerie Pasquetto</name></author><author><name sortKey="Moutaftsi, Magdalini" sort="Moutaftsi, Magdalini" uniqKey="Moutaftsi M" first="Magdalini" last="Moutaftsi">Magdalini Moutaftsi</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Sidney, John" sort="Sidney, John" uniqKey="Sidney J" first="John" last="Sidney">John Sidney</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Panchanathan, Vijay" sort="Panchanathan, Vijay" uniqKey="Panchanathan V" first="Vijay" last="Panchanathan">Vijay Panchanathan</name><affiliation><nlm:aff id="A2"> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</nlm:aff></affiliation></author><author><name sortKey="Tscharke, David C" sort="Tscharke, David C" uniqKey="Tscharke D" first="David C." last="Tscharke">David C. Tscharke</name><affiliation><nlm:aff id="A2"> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</nlm:aff></affiliation></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillere">Bernard Maillere</name><affiliation><nlm:aff id="A3"> Institut de Biologie et Technologies de Saclay, Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif sur Yvette, France</nlm:aff></affiliation></author><author><name sortKey="Grey, Howard" sort="Grey, Howard" uniqKey="Grey H" first="Howard" last="Grey">Howard Grey</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Understanding immunity to vaccinia virus (VACV) is important for the development of safer vaccines for smallpox- and poxvirus-vectored recombinant vaccines. VACV is also emerging as an outstanding model for studying CD8<sup>+</sup> T cell immunodominance because of the large number of CD8<sup>+</sup> T cell epitopes known for this virus in both mice and humans. In this study, we characterize the CD8<sup>+</sup> T cell response in vaccinated BALB/c mice by a genome-wide mapping approach. Responses to each of 54 newly identified H-2<sup>d</sup>-restricted T cell epitopes could be detected after i.p. and dermal vaccination routes. Analysis of these new epitopes in the context of those already known for VACV in mice and humans revealed two important findings. First, CD8<sup>+</sup> T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes. Second, some proteins constituted the major targets of the immune response by a specific haplotype as they recruited the majority of the specific CD8<sup>+</sup> T cells but these proteins did not correspond to the immunoprevalent Ags. Thus, we found a dissociation between immunoprevalence and immunodominance, implying that different sets of rules govern these two phenomena. Together, these findings have clear implications for the design of CD8<sup>+</sup> T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2985117R</journal-id><journal-id journal-id-type="pubmed-jr-id">4816</journal-id><journal-id journal-id-type="nlm-ta">J Immunol</journal-id><journal-title>Journal of immunology (Baltimore, Md. : 1950)</journal-title><issn pub-type="ppub">0022-1767</issn><issn pub-type="epub">1550-6606</issn></journal-meta><article-meta><article-id pub-id-type="pmid">18490718</article-id><article-id pub-id-type="pmc">2533852</article-id><article-id pub-id-type="manuscript">NIHMS63362</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve<xref rid="FN2" ref-type="fn">1</xref></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Oseroff</surname><given-names>Carla</given-names></name><xref rid="A1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Peters</surname><given-names>Bjoern</given-names></name><xref rid="A1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Pasquetto</surname><given-names>Valerie</given-names></name></contrib><contrib contrib-type="author"><name><surname>Moutaftsi</surname><given-names>Magdalini</given-names></name><xref rid="A1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Sidney</surname><given-names>John</given-names></name><xref rid="A1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Panchanathan</surname><given-names>Vijay</given-names></name><xref rid="A2" ref-type="aff">†</xref></contrib><contrib contrib-type="author"><name><surname>Tscharke</surname><given-names>David C.</given-names></name><xref rid="A2" ref-type="aff">†</xref></contrib><contrib contrib-type="author"><name><surname>Maillere</surname><given-names>Bernard</given-names></name><xref rid="A3" ref-type="aff">‡</xref></contrib><contrib contrib-type="author"><name><surname>Grey</surname><given-names>Howard</given-names></name><xref rid="A1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Sette</surname><given-names>Alessandro</given-names></name><xref rid="A1" ref-type="aff">*</xref><xref rid="FN1" ref-type="author-notes">2</xref></contrib></contrib-group><aff id="A1"><label>*</label> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</aff><aff id="A2"><label>†</label> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</aff><aff id="A3"><label>‡</label> Institut de Biologie et Technologies de Saclay, Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif sur Yvette, France</aff><author-notes><corresp id="FN1"><label>2</label>Address correspondence and reprint requests to Dr. Alessandro Sette, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. E-mail address: <email>alex@liai.org</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>15</day><month>8</month><year>2008</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>6</month><year>2008</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>6</month><year>2009</year></pub-date><volume>180</volume><issue>11</issue><fpage>7193</fpage><lpage>7202</lpage><abstract><p id="P1">Understanding immunity to vaccinia virus (VACV) is important for the development of safer vaccines for smallpox- and poxvirus-vectored recombinant vaccines. VACV is also emerging as an outstanding model for studying CD8<sup>+</sup> T cell immunodominance because of the large number of CD8<sup>+</sup> T cell epitopes known for this virus in both mice and humans. In this study, we characterize the CD8<sup>+</sup> T cell response in vaccinated BALB/c mice by a genome-wide mapping approach. Responses to each of 54 newly identified H-2<sup>d</sup>-restricted T cell epitopes could be detected after i.p. and dermal vaccination routes. Analysis of these new epitopes in the context of those already known for VACV in mice and humans revealed two important findings. First, CD8<sup>+</sup> T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes. Second, some proteins constituted the major targets of the immune response by a specific haplotype as they recruited the majority of the specific CD8<sup>+</sup> T cells but these proteins did not correspond to the immunoprevalent Ags. Thus, we found a dissociation between immunoprevalence and immunodominance, implying that different sets of rules govern these two phenomena. Together, these findings have clear implications for the design of CD8<sup>+</sup> T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.</p></abstract><contract-num rid="AI1">R01 AI056268-04</contract-num><contract-sponsor id="AI1">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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