Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities
Identifieur interne : 000758 ( Pmc/Curation ); précédent : 000757; suivant : 000759Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities
Auteurs : Sergio Qui Ones-Parra [Australie] ; Emma Grant [Australie] ; Liyen Loh [Australie] ; Thi H. O. Nguyen [Australie] ; Kristy-Anne Campbell [Australie] ; Steven Y. C. Tong [Australie] ; Adrian Miller [Australie] ; Peter C. Doherty [Australie, États-Unis] ; Dhanasekaran Vijaykrishna ; Jamie Rossjohn [Australie, Royaume-Uni] ; Stephanie Gras [Australie] ; Katherine Kedzierska [Australie]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
The severity of the novel H7N9 influenza A virus (IAV) and the lack of neutralizing antibodies raise real pandemic concerns. In this scenario, CD8+ T lymphocytes (CTLs) may provide a layer of protection against the H7N9 virus. Our study dissects the extent of preexisting CTL immunity with the potential to respond to H7N9. We identified conserved immunogenic peptides with the capacity to elicit robust CTL responses against any human IAV, including the H7N9 virus, as well as the mutations that abolish CTL recognition. The human leukocyte antigen class I molecules that present these peptides vary in prevalence depending on the ethnicity. Such analyses found that the Alaskan and Australian Indigenous people may be particularly vulnerable to the H7N9 influenza disease.
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DOI: 10.1073/pnas.1322229111
PubMed: 24395804
PubMed Central: 3903243
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Dhanasekaran Vijaykrishna<affiliation><nlm:aff wicri:cut="; and" id="aff7">Laboratory of Virus Evolution, Program in Emerging Infectious Diseases, Duke–National University of Singapore Graduate Medical School, Republic of Singapore 169857</nlm:aff><wicri:noCountry code="subfield">Republic of Singapore 169857</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Preexisting CD8<sup>+</sup> T-cell immunity to the H7N9 influenza A virus varies across ethnicities</title><author><name sortKey="Qui Ones Parra, Sergio" sort="Qui Ones Parra, Sergio" uniqKey="Qui Ones Parra S" first="Sergio" last="Qui Ones-Parra">Sergio Qui Ones-Parra</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Grant, Emma" sort="Grant, Emma" uniqKey="Grant E" first="Emma" last="Grant">Emma Grant</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Loh, Liyen" sort="Loh, Liyen" uniqKey="Loh L" first="Liyen" last="Loh">Liyen Loh</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Nguyen, Thi H O" sort="Nguyen, Thi H O" uniqKey="Nguyen T" first="Thi H. O." last="Nguyen">Thi H. O. Nguyen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicine, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC 3004, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC 3004</wicri:regionArea></affiliation></author><author><name sortKey="Campbell, Kristy Anne" sort="Campbell, Kristy Anne" uniqKey="Campbell K" first="Kristy-Anne" last="Campbell">Kristy-Anne Campbell</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation></author><author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y. C." last="Tong">Steven Y. C. Tong</name><affiliation wicri:level="1"><nlm:aff id="aff4">Menzies School of Health and Research, Charles Darwin University, Causarina, NT 0811, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Menzies School of Health and Research, Charles Darwin University, Causarina, NT 0811</wicri:regionArea></affiliation></author><author><name sortKey="Miller, Adrian" sort="Miller, Adrian" uniqKey="Miller A" first="Adrian" last="Miller">Adrian Miller</name><affiliation wicri:level="1"><nlm:aff id="aff5">Indigenous Research Network, Griffith University, Brisbane, QLD 4111, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Indigenous Research Network, Griffith University, Brisbane, QLD 4111</wicri:regionArea></affiliation></author><author><name sortKey="Doherty, Peter C" sort="Doherty, Peter C" uniqKey="Doherty P" first="Peter C." last="Doherty">Peter C. Doherty</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Immunology, St. Jude Children’s Research Hospital, Memphis</wicri:cityArea></affiliation></author><author><name sortKey="Vijaykrishna, Dhanasekaran" sort="Vijaykrishna, Dhanasekaran" uniqKey="Vijaykrishna D" first="Dhanasekaran" last="Vijaykrishna">Dhanasekaran Vijaykrishna</name><affiliation><nlm:aff wicri:cut="; and" id="aff7">Laboratory of Virus Evolution, Program in Emerging Infectious Diseases, Duke–National University of Singapore Graduate Medical School, Republic of Singapore 169857</nlm:aff><wicri:noCountry code="subfield">Republic of Singapore 169857</wicri:noCountry></affiliation></author><author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8">Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN</wicri:regionArea></affiliation></author><author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stephanie" last="Gras">Stephanie Gras</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation></author><author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24395804</idno><idno type="pmc">3903243</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903243</idno><idno type="RBID">PMC:3903243</idno><idno type="doi">10.1073/pnas.1322229111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000758</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000758</idno><idno type="wicri:Area/Pmc/Curation">000758</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000758</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Preexisting CD8<sup>+</sup> T-cell immunity to the H7N9 influenza A virus varies across ethnicities</title><author><name sortKey="Qui Ones Parra, Sergio" sort="Qui Ones Parra, Sergio" uniqKey="Qui Ones Parra S" first="Sergio" last="Qui Ones-Parra">Sergio Qui Ones-Parra</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Grant, Emma" sort="Grant, Emma" uniqKey="Grant E" first="Emma" last="Grant">Emma Grant</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Loh, Liyen" sort="Loh, Liyen" uniqKey="Loh L" first="Liyen" last="Loh">Liyen Loh</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Nguyen, Thi H O" sort="Nguyen, Thi H O" uniqKey="Nguyen T" first="Thi H. O." last="Nguyen">Thi H. O. Nguyen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Medicine, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC 3004, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC 3004</wicri:regionArea></affiliation></author><author><name sortKey="Campbell, Kristy Anne" sort="Campbell, Kristy Anne" uniqKey="Campbell K" first="Kristy-Anne" last="Campbell">Kristy-Anne Campbell</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation></author><author><name sortKey="Tong, Steven Y C" sort="Tong, Steven Y C" uniqKey="Tong S" first="Steven Y. C." last="Tong">Steven Y. C. Tong</name><affiliation wicri:level="1"><nlm:aff id="aff4">Menzies School of Health and Research, Charles Darwin University, Causarina, NT 0811, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Menzies School of Health and Research, Charles Darwin University, Causarina, NT 0811</wicri:regionArea></affiliation></author><author><name sortKey="Miller, Adrian" sort="Miller, Adrian" uniqKey="Miller A" first="Adrian" last="Miller">Adrian Miller</name><affiliation wicri:level="1"><nlm:aff id="aff5">Indigenous Research Network, Griffith University, Brisbane, QLD 4111, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Indigenous Research Network, Griffith University, Brisbane, QLD 4111</wicri:regionArea></affiliation></author><author><name sortKey="Doherty, Peter C" sort="Doherty, Peter C" uniqKey="Doherty P" first="Peter C." last="Doherty">Peter C. Doherty</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation><affiliation wicri:level="2"><nlm:aff id="aff6">Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Immunology, St. Jude Children’s Research Hospital, Memphis</wicri:cityArea></affiliation></author><author><name sortKey="Vijaykrishna, Dhanasekaran" sort="Vijaykrishna, Dhanasekaran" uniqKey="Vijaykrishna D" first="Dhanasekaran" last="Vijaykrishna">Dhanasekaran Vijaykrishna</name><affiliation><nlm:aff wicri:cut="; and" id="aff7">Laboratory of Virus Evolution, Program in Emerging Infectious Diseases, Duke–National University of Singapore Graduate Medical School, Republic of Singapore 169857</nlm:aff><wicri:noCountry code="subfield">Republic of Singapore 169857</wicri:noCountry></affiliation></author><author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8">Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN</wicri:regionArea></affiliation></author><author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stephanie" last="Gras">Stephanie Gras</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea></affiliation></author><author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>The severity of the novel H7N9 influenza A virus (IAV) and the lack of neutralizing antibodies raise real pandemic concerns. In this scenario, CD8<sup>+</sup> T lymphocytes (CTLs) may provide a layer of protection against the H7N9 virus. Our study dissects the extent of preexisting CTL immunity with the potential to respond to H7N9. We identified conserved immunogenic peptides with the capacity to elicit robust CTL responses against any human IAV, including the H7N9 virus, as well as the mutations that abolish CTL recognition. The human leukocyte antigen class I molecules that present these peptides vary in prevalence depending on the ethnicity. Such analyses found that the Alaskan and Australian Indigenous people may be particularly vulnerable to the H7N9 influenza disease.</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">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24395804</article-id><article-id pub-id-type="pmc">3903243</article-id><article-id pub-id-type="publisher-id">201322229</article-id><article-id pub-id-type="doi">10.1073/pnas.1322229111</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Immunology</subject></subj-group></subj-group><series-title>From the Cover</series-title></article-categories><title-group><article-title>Preexisting CD8<sup>+</sup> T-cell immunity to the H7N9 influenza A virus varies across ethnicities</article-title><alt-title alt-title-type="short">CD8 T-cell immunity, H7N9 infection, and HLA types</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Quiñones-Parra</surname><given-names>Sergio</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grant</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Loh</surname><given-names>Liyen</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nguyen</surname><given-names>Thi H. O.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Campbell</surname><given-names>Kristy-Anne</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tong</surname><given-names>Steven Y. C.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Adrian</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Doherty</surname><given-names>Peter C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vijaykrishna</surname><given-names>Dhanasekaran</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rossjohn</surname><given-names>Jamie</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gras</surname><given-names>Stephanie</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kedzierska</surname><given-names>Katherine</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3010, Australia;</aff><aff id="aff2"><sup>b</sup>Department of Medicine, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC 3004, Australia;</aff><aff id="aff3"><sup>c</sup>Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;</aff><aff id="aff4"><sup>d</sup>Menzies School of Health and Research, Charles Darwin University, Causarina, NT 0811, Australia;</aff><aff id="aff5"><sup>e</sup>Indigenous Research Network, Griffith University, Brisbane, QLD 4111, Australia;</aff><aff id="aff6"><sup>f</sup>Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105;</aff><aff id="aff7"><sup>g</sup>Laboratory of Virus Evolution, Program in Emerging Infectious Diseases, Duke–National University of Singapore Graduate Medical School, Republic of Singapore 169857; and</aff><aff id="aff8"><sup>h</sup>Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed. E-mail: <email>pcd@unimelb.edu.au</email> or <email>kkedz@unimelb.edu.au</email>.</corresp><fn fn-type="edited-by"><p>Contributed by Peter C. Doherty, December 4, 2013 (sent for review November 8, 2013)</p></fn><fn fn-type="con"><p>Author contributions: S.Q.-P., E.G., L.L., P.C.D., S.G., and K.K. designed research; S.Q.-P., E.G., L.L., T.H.O.N., K.-A.C., D.V., and S.G. performed research; S.Q.-P., E.G., L.L., D.V., S.G., and K.K. analyzed data; and S.Q.-P., S.Y.C.T., A.M., P.C.D., D.V., J.R., S.G., and K.K. wrote the paper.</p></fn><fn fn-type="conflict"><p>The authors declare no conflict of interest.</p></fn></author-notes><pub-date pub-type="ppub"><day>21</day><month>1</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>6</day><month>1</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>6</day><month>1</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>111</volume><issue>3</issue><fpage>1049</fpage><lpage>1054</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201322229.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Significance</title><p>The severity of the novel H7N9 influenza A virus (IAV) and the lack of neutralizing antibodies raise real pandemic concerns. In this scenario, CD8<sup>+</sup> T lymphocytes (CTLs) may provide a layer of protection against the H7N9 virus. Our study dissects the extent of preexisting CTL immunity with the potential to respond to H7N9. We identified conserved immunogenic peptides with the capacity to elicit robust CTL responses against any human IAV, including the H7N9 virus, as well as the mutations that abolish CTL recognition. The human leukocyte antigen class I molecules that present these peptides vary in prevalence depending on the ethnicity. Such analyses found that the Alaskan and Australian Indigenous people may be particularly vulnerable to the H7N9 influenza disease.</p></abstract><abstract><p>The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus–specific CD8<sup>+</sup> T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16–57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701<sub>,</sub> B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.</p></abstract><kwd-group><kwd>CD8 T cells</kwd><kwd>HLA types</kwd></kwd-group><counts><page-count count="6"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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