Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.
Identifieur interne : 001511 ( Main/Merge ); précédent : 001510; suivant : 001512Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals.
Auteurs : Chao Wu [République populaire de Chine] ; 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.
Descripteurs français
- KwdFr :
- Agranulocytes (cytologie), Antigène HLA-A2 (génétique), Antigène HLA-A2 (immunologie), Biologie informatique (), Déterminants antigéniques des lymphocytes T (), Humains, Immunothérapie (), Interféron gamma (métabolisme), Lymphocytes T CD8+ (cytologie), Nucléoprotéines (métabolisme), Orthomyxoviridae (métabolisme), Peptides (), Virus (métabolisme), Virus de la grippe A (métabolisme), Épitopes (), Épitopes immunodominants (immunologie).
- MESH :
- cytologie : Agranulocytes, Lymphocytes T CD8+.
- génétique : Antigène HLA-A2.
- immunologie : Antigène HLA-A2, Épitopes immunodominants.
- métabolisme : Interféron gamma, Nucléoprotéines, Orthomyxoviridae, Virus, Virus de la grippe A.
- Biologie informatique, Déterminants antigéniques des lymphocytes T, Humains, Immunothérapie, Peptides, Épitopes.
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></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="KwdFr" xml:lang="fr"><term>Agranulocytes (cytologie)</term><term>Antigène HLA-A2 (génétique)</term><term>Antigène HLA-A2 (immunologie)</term><term>Biologie informatique ()</term><term>Déterminants antigéniques des lymphocytes T ()</term><term>Humains</term><term>Immunothérapie ()</term><term>Interféron gamma (métabolisme)</term><term>Lymphocytes T CD8+ (cytologie)</term><term>Nucléoprotéines (métabolisme)</term><term>Orthomyxoviridae (métabolisme)</term><term>Peptides ()</term><term>Virus (métabolisme)</term><term>Virus de la grippe A (métabolisme)</term><term>Épitopes ()</term><term>Épitopes immunodominants (immunologie)</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="cytologie" xml:lang="fr"><term>Agranulocytes</term><term>Lymphocytes T CD8+</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" qualifier="génétique" xml:lang="fr"><term>Antigène HLA-A2</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigène HLA-A2</term><term>Épitopes immunodominants</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" qualifier="métabolisme" xml:lang="fr"><term>Interféron gamma</term><term>Nucléoprotéines</term><term>Orthomyxoviridae</term><term>Virus</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biologie informatique</term><term>Déterminants antigéniques des lymphocytes T</term><term>Humains</term><term>Immunothérapie</term><term>Peptides</term><term>Épitopes</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></record>Pour manipuler ce document sous Unix (Dilib)
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