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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals</title>
<author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Shihong" sort="Zhang, Shihong" uniqKey="Zhang S" first="Shihong" last="Zhang">Shihong Zhang</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tan, Shuguang" sort="Tan, Shuguang" uniqKey="Tan S" first="Shuguang" last="Tan">Shuguang Tan</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yi, Yong" sort="Yi, Yong" uniqKey="Yi Y" first="Yong" last="Yi">Yong Yi</name>
<affiliation><nlm:aff id="aff4">306th Hospital of PLA, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Bin" sort="Wu, Bin" uniqKey="Wu B" first="Bin" last="Wu">Bin Wu</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cao, Bin" sort="Cao, Bin" uniqKey="Cao B" first="Bin" last="Cao">Bin Cao</name>
<affiliation><nlm:aff id="aff6">Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Fengcai" sort="Zhu, Fengcai" uniqKey="Zhu F" first="Fengcai" last="Zhu">Fengcai Zhu</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name>
<affiliation><nlm:aff id="aff6">Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff7">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23015716</idno>
<idno type="pmc">3503122</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503122</idno>
<idno type="RBID">PMC:3503122</idno>
<idno type="doi">10.1128/JVI.01841-12</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000657</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals</title>
<author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Shihong" sort="Zhang, Shihong" uniqKey="Zhang S" first="Shihong" last="Zhang">Shihong Zhang</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tan, Shuguang" sort="Tan, Shuguang" uniqKey="Tan S" first="Shuguang" last="Tan">Shuguang Tan</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yi, Yong" sort="Yi, Yong" uniqKey="Yi Y" first="Yong" last="Yi">Yong Yi</name>
<affiliation><nlm:aff id="aff4">306th Hospital of PLA, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Bin" sort="Wu, Bin" uniqKey="Wu B" first="Bin" last="Wu">Bin Wu</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cao, Bin" sort="Cao, Bin" uniqKey="Cao B" first="Bin" last="Cao">Bin Cao</name>
<affiliation><nlm:aff id="aff6">Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Fengcai" sort="Zhu, Fengcai" uniqKey="Zhu F" first="Fengcai" last="Zhu">Fengcai Zhu</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Chen" sort="Wang, Chen" uniqKey="Wang C" first="Chen" last="Wang">Chen Wang</name>
<affiliation><nlm:aff id="aff6">Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name>
<affiliation><nlm:aff id="aff5">Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation><nlm:aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff7">Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p>Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24<sup>+</sup>
population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11<sup>+</sup>
and HLA-A24<sup>+</sup>
donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11<sup>+</sup>
population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.</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 Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23015716</article-id>
<article-id pub-id-type="pmc">3503122</article-id>
<article-id pub-id-type="publisher-id">01841-12</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01841-12</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Jun</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>Zhang</surname>
<given-names>Shihong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tan</surname>
<given-names>Shuguang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yi</surname>
<given-names>Yong</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Bin</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cao</surname>
<given-names>Bin</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhu</surname>
<given-names>Fengcai</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Chen</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Hua</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Qi</surname>
<given-names>Jianxun</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" corresp="yes"><name><surname>Gao</surname>
<given-names>George F.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</aff>
<aff id="aff2"><label>b</label>
China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China</aff>
<aff id="aff3"><label>c</label>
College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing, China</aff>
<aff id="aff4"><label>d</label>
306th Hospital of PLA, Beijing, China</aff>
<aff id="aff5"><label>e</label>
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China</aff>
<aff id="aff6"><label>f</label>
Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China</aff>
<aff id="aff7"><label>g</label>
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China</aff>
</contrib-group>
<author-notes><corresp>Address correspondence to George F. Gao, <email>gaof@im.ac.cn</email>
.</corresp>
<fn fn-type="equal"><p>J.L., S.Z., and S.T. contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>12</month>
<year>2012</year>
</pub-date>
<volume>86</volume>
<issue>24</issue>
<fpage>13281</fpage>
<lpage>13294</lpage>
<history><date date-type="received"><day>16</day>
<month>7</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>17</day>
<month>9</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv02412013281.pdf"></self-uri>
<abstract><p>Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24<sup>+</sup>
population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11<sup>+</sup>
and HLA-A24<sup>+</sup>
donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11<sup>+</sup>
population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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