Engineering T cells specific for a dominant severe acute respiratory syndrome coronavirus CD8 T cell epitope.
Identifieur interne : 002120 ( Main/Exploration ); précédent : 002119; suivant : 002121Engineering T cells specific for a dominant severe acute respiratory syndrome coronavirus CD8 T cell epitope.
Auteurs : Hsueh-Ling Janice Oh [Singapour] ; Adeline Chia ; Cynthia Xin Lei Chang ; Hoe Nam Leong ; Khoon Lin Ling ; Gijsbert M. Grotenbreg ; Adam J. Gehring ; Yee Joo Tan ; Antonio BertolettiSource :
- Journal of virology [ 1098-5514 ] ; 2011.
Descripteurs français
- KwdFr :
- Chimiokine CCL3 (métabolisme), Chimiokine CCL4 (métabolisme), Dégranulation cellulaire, Déterminants antigéniques des lymphocytes T (immunologie), Facteur de nécrose tumorale alpha (métabolisme), Génie génétique, Humains, Interféron gamma (métabolisme), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD8+ (immunologie), Mémoire immunologique, Récepteurs aux antigènes des cellules T (génétique), Virus du SRAS (immunologie), Épitopes immunodominants (immunologie).
- MESH :
- génétique : Récepteurs aux antigènes des cellules T.
- immunologie : Déterminants antigéniques des lymphocytes T, Lymphocytes T CD4+, Lymphocytes T CD8+, Virus du SRAS, Épitopes immunodominants.
- métabolisme : Chimiokine CCL3, Chimiokine CCL4, Facteur de nécrose tumorale alpha, Interféron gamma.
- Dégranulation cellulaire, Génie génétique, Humains, Mémoire immunologique.
English descriptors
- KwdEn :
- CD4-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (immunology), Cell Degranulation, Chemokine CCL3 (metabolism), Chemokine CCL4 (metabolism), Epitopes, T-Lymphocyte (immunology), Genetic Engineering, Humans, Immunodominant Epitopes (immunology), Immunologic Memory, Interferon-gamma (metabolism), Receptors, Antigen, T-Cell (genetics), SARS Virus (immunology), Tumor Necrosis Factor-alpha (metabolism).
- MESH :
- chemical , genetics : Receptors, Antigen, T-Cell.
- chemical , immunology : Epitopes, T-Lymphocyte, Immunodominant Epitopes.
- chemical , metabolism : Chemokine CCL3, Chemokine CCL4, Interferon-gamma, Tumor Necrosis Factor-alpha.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, SARS Virus.
- Cell Degranulation, Genetic Engineering, Humans, Immunologic Memory.
Abstract
Severe acute respiratory syndrome (SARS) is a highly contagious and life threatening disease, with a fatality rate of almost 10%. The etiologic agent is a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), with animal reservoirs found in bats and other wild animals and thus the possibility of reemergence. In this study, we first investigated at 6 years postinfection whether SARS-specific memory T cells persist in SARS-recovered individuals, demonstrating that these subjects still possess polyfunctional SARS-specific memory CD4+ and CD8+ T cells. A dominant memory CD8+ T cell response against SARS-CoV nucleocaspid protein (NP; amino acids 216 to 225) was then defined in SARS-recovered individuals carrying HLA-B*40:01, a HLA-B molecule present in approximately one-quarter of subjects of Asian ethnicities. To reconstitute such a CD8+ T cell response, we isolated the alpha and beta T cell receptors of the HLA-B*40:01-restricted SARS-specific CD8+ T cells. Using T cell receptor gene transfer, we generated SARS-specific redirected T cells from the lymphocytes of normal individuals. These engineered CD8+ T cells displayed avidity and functionality similar to that of natural SARS-specific memory CD8+ T cells. They were able to degranulate and produce gamma interferon, tumor necrosis factor alpha, and macrophage inflammatory proteins 1α and 1β after antigenic stimulation. Since there is no effective treatment against SARS, these transduced T cells specific for an immunodominant SARS epitope may provide a new avenue for treatment during a SARS outbreak.
DOI: 10.1128/JVI.05039-11
PubMed: 21813600
Affiliations:
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Le document en format XML
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Gehring</name></author><author><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee Joo" last="Tan">Yee Joo Tan</name></author><author><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21813600</idno><idno type="pmid">21813600</idno><idno type="doi">10.1128/JVI.05039-11</idno><idno type="wicri:Area/PubMed/Corpus">001484</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001484</idno><idno type="wicri:Area/PubMed/Curation">001484</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001484</idno><idno type="wicri:Area/PubMed/Checkpoint">001500</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001500</idno><idno type="wicri:Area/Ncbi/Merge">002371</idno><idno type="wicri:Area/Ncbi/Curation">002371</idno><idno type="wicri:Area/Ncbi/Checkpoint">002371</idno><idno type="wicri:Area/Main/Merge">002146</idno><idno type="wicri:Area/Main/Curation">002120</idno><idno type="wicri:Area/Main/Exploration">002120</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Engineering T cells specific for a dominant severe acute respiratory syndrome coronavirus CD8 T cell epitope.</title><author><name sortKey="Oh, Hsueh Ling Janice" sort="Oh, Hsueh Ling Janice" uniqKey="Oh H" first="Hsueh-Ling Janice" last="Oh">Hsueh-Ling Janice Oh</name><affiliation wicri:level="1"><nlm:affiliation>Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research</wicri:regionArea><wicri:noRegion>Technology and Research</wicri:noRegion></affiliation></author><author><name sortKey="Chia, Adeline" sort="Chia, Adeline" uniqKey="Chia A" first="Adeline" last="Chia">Adeline Chia</name></author><author><name sortKey="Chang, Cynthia Xin Lei" sort="Chang, Cynthia Xin Lei" uniqKey="Chang C" first="Cynthia Xin Lei" last="Chang">Cynthia Xin Lei Chang</name></author><author><name sortKey="Leong, Hoe Nam" sort="Leong, Hoe Nam" uniqKey="Leong H" first="Hoe Nam" last="Leong">Hoe Nam Leong</name></author><author><name sortKey="Ling, Khoon Lin" sort="Ling, Khoon Lin" uniqKey="Ling K" first="Khoon Lin" last="Ling">Khoon Lin Ling</name></author><author><name sortKey="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M" last="Grotenbreg">Gijsbert M. Grotenbreg</name></author><author><name sortKey="Gehring, Adam J" sort="Gehring, Adam J" uniqKey="Gehring A" first="Adam J" last="Gehring">Adam J. Gehring</name></author><author><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee Joo" last="Tan">Yee Joo Tan</name></author><author><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cell Degranulation</term><term>Chemokine CCL3 (metabolism)</term><term>Chemokine CCL4 (metabolism)</term><term>Epitopes, T-Lymphocyte (immunology)</term><term>Genetic Engineering</term><term>Humans</term><term>Immunodominant Epitopes (immunology)</term><term>Immunologic Memory</term><term>Interferon-gamma (metabolism)</term><term>Receptors, Antigen, T-Cell (genetics)</term><term>SARS Virus (immunology)</term><term>Tumor Necrosis Factor-alpha (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Chimiokine CCL3 (métabolisme)</term><term>Chimiokine CCL4 (métabolisme)</term><term>Dégranulation cellulaire</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Facteur de nécrose tumorale alpha (métabolisme)</term><term>Génie génétique</term><term>Humains</term><term>Interféron gamma (métabolisme)</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Mémoire immunologique</term><term>Récepteurs aux antigènes des cellules T (génétique)</term><term>Virus du SRAS (immunologie)</term><term>Épitopes immunodominants (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Antigen, T-Cell</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Immunodominant Epitopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chemokine CCL3</term><term>Chemokine CCL4</term><term>Interferon-gamma</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Récepteurs aux antigènes des cellules T</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term><term>Virus du SRAS</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>CD8-Positive T-Lymphocytes</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Chimiokine CCL3</term><term>Chimiokine CCL4</term><term>Facteur de nécrose tumorale alpha</term><term>Interféron gamma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Degranulation</term><term>Genetic Engineering</term><term>Humans</term><term>Immunologic Memory</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Dégranulation cellulaire</term><term>Génie génétique</term><term>Humains</term><term>Mémoire immunologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a highly contagious and life threatening disease, with a fatality rate of almost 10%. The etiologic agent is a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), with animal reservoirs found in bats and other wild animals and thus the possibility of reemergence. In this study, we first investigated at 6 years postinfection whether SARS-specific memory T cells persist in SARS-recovered individuals, demonstrating that these subjects still possess polyfunctional SARS-specific memory CD4+ and CD8+ T cells. A dominant memory CD8+ T cell response against SARS-CoV nucleocaspid protein (NP; amino acids 216 to 225) was then defined in SARS-recovered individuals carrying HLA-B*40:01, a HLA-B molecule present in approximately one-quarter of subjects of Asian ethnicities. To reconstitute such a CD8+ T cell response, we isolated the alpha and beta T cell receptors of the HLA-B*40:01-restricted SARS-specific CD8+ T cells. Using T cell receptor gene transfer, we generated SARS-specific redirected T cells from the lymphocytes of normal individuals. These engineered CD8+ T cells displayed avidity and functionality similar to that of natural SARS-specific memory CD8+ T cells. They were able to degranulate and produce gamma interferon, tumor necrosis factor alpha, and macrophage inflammatory proteins 1α and 1β after antigenic stimulation. Since there is no effective treatment against SARS, these transduced T cells specific for an immunodominant SARS epitope may provide a new avenue for treatment during a SARS outbreak.</div></front></TEI><affiliations><list><country><li>Singapour</li></country></list><tree><noCountry><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name><name sortKey="Chang, Cynthia Xin Lei" sort="Chang, Cynthia Xin Lei" uniqKey="Chang C" first="Cynthia Xin Lei" last="Chang">Cynthia Xin Lei Chang</name><name sortKey="Chia, Adeline" sort="Chia, Adeline" uniqKey="Chia A" first="Adeline" last="Chia">Adeline Chia</name><name sortKey="Gehring, Adam J" sort="Gehring, Adam J" uniqKey="Gehring A" first="Adam J" last="Gehring">Adam J. Gehring</name><name sortKey="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M" last="Grotenbreg">Gijsbert M. Grotenbreg</name><name sortKey="Leong, Hoe Nam" sort="Leong, Hoe Nam" uniqKey="Leong H" first="Hoe Nam" last="Leong">Hoe Nam Leong</name><name sortKey="Ling, Khoon Lin" sort="Ling, Khoon Lin" uniqKey="Ling K" first="Khoon Lin" last="Ling">Khoon Lin Ling</name><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee Joo" last="Tan">Yee Joo Tan</name></noCountry><country name="Singapour"><noRegion><name sortKey="Oh, Hsueh Ling Janice" sort="Oh, Hsueh Ling Janice" uniqKey="Oh H" first="Hsueh-Ling Janice" last="Oh">Hsueh-Ling Janice Oh</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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