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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cross-reactive CD8<sup>+</sup>
T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses</title>
<author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stephanie" last="Gras">Stephanie Gras</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kedzierski, Lukasz" sort="Kedzierski, Lukasz" uniqKey="Kedzierski L" first="Lukasz" last="Kedzierski">Lukasz Kedzierski</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Valkenburg, Sophie A" sort="Valkenburg, Sophie A" uniqKey="Valkenburg S" first="Sophie A." last="Valkenburg">Sophie A. Valkenburg</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name>
<affiliation><nlm:aff id="aff3"><institution>World Health Organization Collaborating Centre for Reference and Research on Influenza</institution>
, North Melbourne, Victoria 3051,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Yu Chih" sort="Liu, Yu Chih" uniqKey="Liu Y" first="Yu Chih" last="Liu">Yu Chih Liu</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Denholm, Justin T" sort="Denholm, Justin T" uniqKey="Denholm J" first="Justin T." last="Denholm">Justin T. Denholm</name>
<affiliation><nlm:aff id="aff4">Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richards, Michael J" sort="Richards, Michael J" uniqKey="Richards M" first="Michael J." last="Richards">Michael J. Richards</name>
<affiliation><nlm:aff id="aff4">Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff5">Department of Virology,<institution>Erasmus Medical Center</institution>
, 3000 CA Rotterdam,<country>The Netherlands</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kelso, Anne" sort="Kelso, Anne" uniqKey="Kelso A" first="Anne" last="Kelso">Anne Kelso</name>
<affiliation><nlm:aff id="aff3"><institution>World Health Organization Collaborating Centre for Reference and Research on Influenza</institution>
, North Melbourne, Victoria 3051,<country>Australia</country>
;</nlm:aff>
</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><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6">Department of Immunology,<institution>St. Jude Children's Research Hospital</institution>
, Memphis, TN 38105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20616031</idno>
<idno type="pmc">2906563</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906563</idno>
<idno type="RBID">PMC:2906563</idno>
<idno type="doi">10.1073/pnas.1007270107</idno>
<date when="2010">2010</date>
<idno type="wicri:Area/Pmc/Corpus">000750</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000750</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cross-reactive CD8<sup>+</sup>
T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses</title>
<author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stephanie" last="Gras">Stephanie Gras</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kedzierski, Lukasz" sort="Kedzierski, Lukasz" uniqKey="Kedzierski L" first="Lukasz" last="Kedzierski">Lukasz Kedzierski</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Valkenburg, Sophie A" sort="Valkenburg, Sophie A" uniqKey="Valkenburg S" first="Sophie A." last="Valkenburg">Sophie A. Valkenburg</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name>
<affiliation><nlm:aff id="aff3"><institution>World Health Organization Collaborating Centre for Reference and Research on Influenza</institution>
, North Melbourne, Victoria 3051,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Yu Chih" sort="Liu, Yu Chih" uniqKey="Liu Y" first="Yu Chih" last="Liu">Yu Chih Liu</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Denholm, Justin T" sort="Denholm, Justin T" uniqKey="Denholm J" first="Justin T." last="Denholm">Justin T. Denholm</name>
<affiliation><nlm:aff id="aff4">Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richards, Michael J" sort="Richards, Michael J" uniqKey="Richards M" first="Michael J." last="Richards">Michael J. Richards</name>
<affiliation><nlm:aff id="aff4">Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff5">Department of Virology,<institution>Erasmus Medical Center</institution>
, 3000 CA Rotterdam,<country>The Netherlands</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kelso, Anne" sort="Kelso, Anne" uniqKey="Kelso A" first="Anne" last="Kelso">Anne Kelso</name>
<affiliation><nlm:aff id="aff3"><institution>World Health Organization Collaborating Centre for Reference and Research on Influenza</institution>
, North Melbourne, Victoria 3051,<country>Australia</country>
;</nlm:aff>
</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><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6">Department of Immunology,<institution>St. Jude Children's Research Hospital</institution>
, Memphis, TN 38105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
<affiliation><nlm:aff id="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
</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="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 “Spanish flu” rather than more recent “seasonal” strains. We present immunological and structural analyses of cross-reactive CD8<sup>+</sup>
T-cell–mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP<sub>418–426</sub>
peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8<sup>+</sup>
T-cell specificity was probed for 12 different NP<sub>418</sub>
mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP<sub>418</sub>
mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP<sub>418</sub>
variant or the 1918-NP<sub>418</sub>
variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8<sup>+</sup>
T cells specific for the 2009-NP<sub>418</sub>
and 1918-NP<sub>418</sub>
epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.</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="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">20616031</article-id>
<article-id pub-id-type="pmc">2906563</article-id>
<article-id pub-id-type="publisher-id">201007270</article-id>
<article-id pub-id-type="doi">10.1073/pnas.1007270107</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Immunology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Cross-reactive CD8<sup>+</sup>
T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Gras</surname>
<given-names>Stephanie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kedzierski</surname>
<given-names>Lukasz</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="author-notes" rid="fn1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Valkenburg</surname>
<given-names>Sophie A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="author-notes" rid="fn1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Laurie</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Yu Chih</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Denholm</surname>
<given-names>Justin T.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Richards</surname>
<given-names>Michael J.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rimmelzwaan</surname>
<given-names>Guus F.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kelso</surname>
<given-names>Anne</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Doherty</surname>
<given-names>Peter C.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Turner</surname>
<given-names>Stephen J.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rossjohn</surname>
<given-names>Jamie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn2"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kedzierska</surname>
<given-names>Katherine</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn2"><sup>3</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</aff>
<aff id="aff2"><sup>b</sup>
Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</aff>
<aff id="aff3"><sup>c</sup>
<institution>World Health Organization Collaborating Centre for Reference and Research on Influenza</institution>
, North Melbourne, Victoria 3051,<country>Australia</country>
;</aff>
<aff id="aff4"><sup>d</sup>
Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</aff>
<aff id="aff5"><sup>e</sup>
Department of Virology,<institution>Erasmus Medical Center</institution>
, 3000 CA Rotterdam,<country>The Netherlands</country>
; and</aff>
<aff id="aff6"><sup>f</sup>
Department of Immunology,<institution>St. Jude Children's Research Hospital</institution>
, Memphis, TN 38105</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>2</sup>
To whom correspondence may be addressed. E-mail: <email>pcd@unimelb.unimelb.edu.au</email>
, <email>kkedz@unimelb.edu.au</email>
, or <email>jamie.rossjohn@med.monash.edu.au</email>
.</corresp>
<fn fn-type="con"><p>Author contributions: S.G., L.K., S.A.V., K.L., J.T.D., M.J.R., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. designed research; S.G., L.K., S.A.V., K.L., Y.C.L., and K.K. performed research; S.G., J.T.D., M.J.R., G.F.R., and J.R. contributed new reagents/analytic tools; S.G., L.K., S.A.V., K.L., J.R., and K.K. analyzed data; and S.G., L.K., S.A.V., J.T.D., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. wrote the paper.</p>
</fn>
<fn id="fn1" fn-type="equal"><p><sup>1</sup>
S.G., L.K., and S.A.V. contributed equally to this work.</p>
</fn>
<fn id="fn2" fn-type="equal"><p><sup>3</sup>
J.R. and K.K. contributed equally to this work.</p>
</fn>
<fn fn-type="edited-by"><p>Contributed by Peter C. Doherty, May 26, 2010 (sent for review April 30, 2010)</p>
</fn>
<fn fn-type="conflict"><p>The authors declare no conflict of interest.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>28</day>
<month>6</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub"><day>13</day>
<month>7</month>
<year>2010</year>
</pub-date>
<volume>107</volume>
<issue>28</issue>
<fpage>12599</fpage>
<lpage>12604</lpage>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201007270.pdf"></self-uri>
<abstract><p>Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 “Spanish flu” rather than more recent “seasonal” strains. We present immunological and structural analyses of cross-reactive CD8<sup>+</sup>
T-cell–mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP<sub>418–426</sub>
peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8<sup>+</sup>
T-cell specificity was probed for 12 different NP<sub>418</sub>
mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP<sub>418</sub>
mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP<sub>418</sub>
variant or the 1918-NP<sub>418</sub>
variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8<sup>+</sup>
T cells specific for the 2009-NP<sub>418</sub>
and 1918-NP<sub>418</sub>
epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.</p>
</abstract>
<kwd-group><kwd>influenza infection</kwd>
<kwd>T-cell responses</kwd>
<kwd>B7 allelic family</kwd>
<kwd>NP418-426 variants</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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