A Human CD4+ T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus
Identifieur interne : 000652 ( Pmc/Curation ); précédent : 000651; suivant : 000653A Human CD4+ T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus
Auteurs : Jenny Aurielle B. Babon [États-Unis] ; John Cruz [États-Unis] ; Francis A. Ennis [États-Unis] ; Liusong Yin [États-Unis] ; Masanori Terajima [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2012.
Abstract
The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4+ T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+ T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had
Url:
DOI: 10.1128/JVI.06325-11
PubMed: 22718815
PubMed Central: 3416118
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Human CD4<sup>+</sup>
T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus</title>
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<series><title level="j">Journal of Virology</title>
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<front><div type="abstract" xml:lang="en"><p>The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4<sup>+</sup>
T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4<sup>+</sup>
T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had <italic>ex vivo</italic>
gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4<sup>+</sup>
T cells, which are cross-reactive to both influenza A and B viruses.</p>
</div>
</front>
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<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>
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<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>
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<article-meta><article-id pub-id-type="pmid">22718815</article-id>
<article-id pub-id-type="pmc">3416118</article-id>
<article-id pub-id-type="publisher-id">06325-11</article-id>
<article-id pub-id-type="doi">10.1128/JVI.06325-11</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>A Human CD4<sup>+</sup>
T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Babon</surname>
<given-names>Jenny Aurielle B.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
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<contrib contrib-type="author"><name><surname>Cruz</surname>
<given-names>John</given-names>
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<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ennis</surname>
<given-names>Francis A.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
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<contrib contrib-type="author"><name><surname>Yin</surname>
<given-names>Liusong</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
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<contrib contrib-type="author" corresp="yes"><name><surname>Terajima</surname>
<given-names>Masanori</given-names>
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<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA</aff>
<aff id="aff2"><label>b</label>
Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts, USA</aff>
<aff id="aff3"><label>c</label>
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA</aff>
</contrib-group>
<author-notes><corresp>Address correspondence to Masanori Terajima, <email>Masanori.Terajima@umassmed.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>9</month>
<year>2012</year>
</pub-date>
<volume>86</volume>
<issue>17</issue>
<fpage>9233</fpage>
<lpage>9243</lpage>
<history><date date-type="received"><day>15</day>
<month>9</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>6</day>
<month>6</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="zjv01712009233.pdf"></self-uri>
<abstract><p>The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4<sup>+</sup>
T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4<sup>+</sup>
T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had <italic>ex vivo</italic>
gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4<sup>+</sup>
T cells, which are cross-reactive to both influenza A and B viruses.</p>
</abstract>
</article-meta>
</front>
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