Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.
Identifieur interne : 000631 ( PubMed/Corpus ); précédent : 000630; suivant : 000632Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.
Auteurs : Chao Wu ; Damien Zanker ; Sophie Valkenburg ; Bee Tan ; Katherine Kedzierska ; Quan Ming Zou ; Peter C. Doherty ; Weisan ChenSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2011.
English descriptors
- KwdEn :
- CD8-Positive T-Lymphocytes (cytology), Computational Biology (methods), Epitopes (chemistry), Epitopes, T-Lymphocyte (chemistry), HLA-A2 Antigen (genetics), HLA-A2 Antigen (immunology), Humans, Immunodominant Epitopes (immunology), Immunotherapy (methods), Influenza A virus (metabolism), Interferon-gamma (metabolism), Leukocytes, Mononuclear (cytology), Nucleoproteins (metabolism), Orthomyxoviridae (metabolism), Peptides (chemistry), Viruses (metabolism).
- MESH :
- chemical , chemistry : Epitopes, Epitopes, T-Lymphocyte, Peptides.
- cytology : CD8-Positive T-Lymphocytes, Leukocytes, Mononuclear.
- chemical , genetics : HLA-A2 Antigen.
- chemical , immunology : HLA-A2 Antigen, Immunodominant Epitopes.
- metabolism : Influenza A virus, Interferon-gamma, Nucleoproteins, Orthomyxoviridae, Viruses.
- methods : Computational Biology, Immunotherapy.
- Humans.
Abstract
Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8(+) T-cell specificities. The analysis targeted healthy HLA-A2(+) donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8(+) T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8(+) T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.
DOI: 10.1073/pnas.1105624108
PubMed: 21562214
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pubmed:21562214Le document en format XML
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Doherty</name></author><author><name sortKey="Chen, Weisan" sort="Chen, Weisan" uniqKey="Chen W" first="Weisan" last="Chen">Weisan Chen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21562214</idno><idno type="pmid">21562214</idno><idno type="doi">10.1073/pnas.1105624108</idno><idno type="wicri:Area/PubMed/Corpus">000631</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000631</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.</title><author><name sortKey="Wu, Chao" sort="Wu, Chao" uniqKey="Wu C" first="Chao" last="Wu">Chao Wu</name><affiliation><nlm:affiliation>Department of Clinical Microbiology and Immunology, Third Military Medical University, Chongqing 400038, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zanker, Damien" sort="Zanker, Damien" uniqKey="Zanker D" first="Damien" last="Zanker">Damien Zanker</name></author><author><name sortKey="Valkenburg, Sophie" sort="Valkenburg, Sophie" uniqKey="Valkenburg S" first="Sophie" last="Valkenburg">Sophie Valkenburg</name></author><author><name sortKey="Tan, Bee" sort="Tan, Bee" uniqKey="Tan B" first="Bee" last="Tan">Bee Tan</name></author><author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name></author><author><name sortKey="Zou, Quan Ming" sort="Zou, Quan Ming" uniqKey="Zou Q" first="Quan Ming" last="Zou">Quan Ming Zou</name></author><author><name sortKey="Doherty, Peter C" sort="Doherty, Peter C" uniqKey="Doherty P" first="Peter C" last="Doherty">Peter C. Doherty</name></author><author><name sortKey="Chen, Weisan" sort="Chen, Weisan" uniqKey="Chen W" first="Weisan" last="Chen">Weisan Chen</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CD8-Positive T-Lymphocytes (cytology)</term><term>Computational Biology (methods)</term><term>Epitopes (chemistry)</term><term>Epitopes, T-Lymphocyte (chemistry)</term><term>HLA-A2 Antigen (genetics)</term><term>HLA-A2 Antigen (immunology)</term><term>Humans</term><term>Immunodominant Epitopes (immunology)</term><term>Immunotherapy (methods)</term><term>Influenza A virus (metabolism)</term><term>Interferon-gamma (metabolism)</term><term>Leukocytes, Mononuclear (cytology)</term><term>Nucleoproteins (metabolism)</term><term>Orthomyxoviridae (metabolism)</term><term>Peptides (chemistry)</term><term>Viruses (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term><term>Epitopes, T-Lymphocyte</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term><term>Leukocytes, Mononuclear</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HLA-A2 Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>HLA-A2 Antigen</term><term>Immunodominant Epitopes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Influenza A virus</term><term>Interferon-gamma</term><term>Nucleoproteins</term><term>Orthomyxoviridae</term><term>Viruses</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Computational Biology</term><term>Immunotherapy</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8(+) T-cell specificities. The analysis targeted healthy HLA-A2(+) donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8(+) T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8(+) T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21562214</PMID><DateCompleted><Year>2011</Year><Month>08</Month><Day>23</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN><JournalIssue CitedMedium="Internet"><Volume>108</Volume><Issue>22</Issue><PubDate><Year>2011</Year><Month>May</Month><Day>31</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc. Natl. Acad. Sci. U.S.A.</ISOAbbreviation></Journal><ArticleTitle>Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.</ArticleTitle><Pagination><MedlinePgn>9178-83</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.1105624108</ELocationID><Abstract><AbstractText>Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8(+) T-cell specificities. The analysis targeted healthy HLA-A2(+) donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8(+) T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8(+) T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Chao</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Clinical Microbiology and Immunology, Third Military Medical University, Chongqing 400038, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zanker</LastName><ForeName>Damien</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Valkenburg</LastName><ForeName>Sophie</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Bee</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Kedzierska</LastName><ForeName>Katherine</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Quan Ming</ForeName><Initials>QM</Initials></Author><Author ValidYN="Y"><LastName>Doherty</LastName><ForeName>Peter C</ForeName><Initials>PC</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Weisan</ForeName><Initials>W</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>05</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Proc Natl Acad Sci U S A</MedlineTA><NlmUniqueID>7505876</NlmUniqueID><ISSNLinking>0027-8424</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000939">Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018984">Epitopes, T-Lymphocyte</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015789">HLA-A2 Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016056">Immunodominant Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009698">Nucleoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>82115-62-6</RegistryNumber><NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019295" MajorTopicYN="N">Computational 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