Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses
Identifieur interne : 000E92 ( Main/Exploration ); précédent : 000E91; suivant : 000E93Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses
Auteurs : Stephanie Gras [Australie] ; Lukasz Kedzierski [Australie] ; Sophie A. Valkenburg [Australie] ; Karen Laurie [Australie] ; Yu Chih Liu [Australie] ; Justin T. Denholm [Australie] ; Michael J. Richards [Australie] ; Guus F. Rimmelzwaan [Pays-Bas] ; Anne Kelso [Australie] ; Peter C. Doherty [Australie, États-Unis] ; Stephen J. Turner [Australie] ; Jamie Rossjohn [Australie] ; Katherine Kedzierska [Australie]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2010.
Abstract
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+ T-cell–mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP418–426 peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8+ T-cell specificity was probed for 12 different NP418 mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP418 mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP418 variant or the 1918-NP418 variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8+ T cells specific for the 2009-NP418 and 1918-NP418 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.
Url:
DOI: 10.1073/pnas.1007270107
PubMed: 20616031
PubMed Central: 2906563
Affiliations:
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T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses</title>
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<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 wicri:level="1"><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>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kedzierski, Lukasz" sort="Kedzierski, Lukasz" uniqKey="Kedzierski L" first="Lukasz" last="Kedzierski">Lukasz Kedzierski</name>
<affiliation wicri:level="1"><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>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><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>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Liu, Yu Chih" sort="Liu, Yu Chih" uniqKey="Liu Y" first="Yu Chih" last="Liu">Yu Chih Liu</name>
<affiliation wicri:level="1"><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>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Denholm, Justin T" sort="Denholm, Justin T" uniqKey="Denholm J" first="Justin T." last="Denholm">Justin T. Denholm</name>
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, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Richards, Michael J" sort="Richards, Michael J" uniqKey="Richards M" first="Michael J." last="Richards">Michael J. Richards</name>
<affiliation wicri:level="1"><nlm:aff id="aff4">Victorian Infectious Diseases Service,<institution>Royal Melbourne Hospital</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff5">Department of Virology,<institution>Erasmus Medical Center</institution>
, 3000 CA Rotterdam,<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kelso, Anne" sort="Kelso, Anne" uniqKey="Kelso A" first="Anne" last="Kelso">Anne Kelso</name>
<affiliation wicri:level="1"><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>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</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="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff6">Department of Immunology,<institution>St. Jude Children's Research Hospital</institution>
, Memphis, TN 38105</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>, Memphis</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</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="aff1">Protein Crystallography Unit, Department of Biochemistry and Molecular Biology,<institution>Monash University</institution>
, Clayton, Victoria 3800,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</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="aff2">Department of Microbiology and Immunology,<institution>University of Melbourne</institution>
, Parkville, Victoria 3010,<country>Australia</country>
;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
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<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>
<affiliations><list><country><li>Australie</li>
<li>Pays-Bas</li>
<li>États-Unis</li>
</country>
<region><li>Tennessee</li>
</region>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stephanie" last="Gras">Stephanie Gras</name>
</noRegion>
<name sortKey="Denholm, Justin T" sort="Denholm, Justin T" uniqKey="Denholm J" first="Justin T." last="Denholm">Justin T. Denholm</name>
<name sortKey="Doherty, Peter C" sort="Doherty, Peter C" uniqKey="Doherty P" first="Peter C." last="Doherty">Peter C. Doherty</name>
<name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<name sortKey="Kedzierski, Lukasz" sort="Kedzierski, Lukasz" uniqKey="Kedzierski L" first="Lukasz" last="Kedzierski">Lukasz Kedzierski</name>
<name sortKey="Kedzierski, Lukasz" sort="Kedzierski, Lukasz" uniqKey="Kedzierski L" first="Lukasz" last="Kedzierski">Lukasz Kedzierski</name>
<name sortKey="Kelso, Anne" sort="Kelso, Anne" uniqKey="Kelso A" first="Anne" last="Kelso">Anne Kelso</name>
<name sortKey="Laurie, Karen" sort="Laurie, Karen" uniqKey="Laurie K" first="Karen" last="Laurie">Karen Laurie</name>
<name sortKey="Liu, Yu Chih" sort="Liu, Yu Chih" uniqKey="Liu Y" first="Yu Chih" last="Liu">Yu Chih Liu</name>
<name sortKey="Richards, Michael J" sort="Richards, Michael J" uniqKey="Richards M" first="Michael J." last="Richards">Michael J. Richards</name>
<name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
<name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name>
<name sortKey="Valkenburg, Sophie A" sort="Valkenburg, Sophie A" uniqKey="Valkenburg S" first="Sophie A." last="Valkenburg">Sophie A. Valkenburg</name>
</country>
<country name="Pays-Bas"><noRegion><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
</noRegion>
</country>
<country name="États-Unis"><region name="Tennessee"><name sortKey="Doherty, Peter C" sort="Doherty, Peter C" uniqKey="Doherty P" first="Peter C." last="Doherty">Peter C. Doherty</name>
</region>
</country>
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</record>
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