Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope
Identifieur interne : 002377 ( Main/Exploration ); précédent : 002376; suivant : 002378Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope
Auteurs : Hsueh-Ling Janice Oh [Singapour] ; Adeline Chia [Singapour] ; CYNTHIA XIN LEI CHANG [Singapour] ; HOE NAM LEONG [Singapour] ; KHOON LIN LING [Singapour] ; Gijsbert M. Grotenbreg [Singapour] ; Adam J. Gehring [Singapour] ; YEE JOO TAN [Singapour] ; Antonio Bertoletti [Singapour]Source :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
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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.
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aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>NUS Graduate School for Integrative Science and Engineering</s1><s2>Singapore</s2><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>NUS Graduate School for Integrative Science and Engineering</wicri:noRegion></affiliation></author><author><name sortKey="Hoe Nam Leong" sort="Hoe Nam Leong" uniqKey="Hoe Nam Leong" last="Hoe Nam Leong">HOE NAM LEONG</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>National University of Singapore</s1><s2>Singapore</s2><s3>SGP</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Khoon Lin Ling" sort="Khoon Lin Ling" uniqKey="Khoon Lin Ling" last="Khoon Lin Ling">KHOON LIN LING</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>National University of Singapore</s1><s2>Singapore</s2><s3>SGP</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M." last="Grotenbreg">Gijsbert M. Grotenbreg</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Agency for Science, Technology and Research</s1><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Agency for Science, Technology and Research</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Microbiology,Department of Biological Sciences</s1><s2>Singapore</s2><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>NUS Graduate School for Integrative Science and Engineering</s1><s2>Singapore</s2><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>NUS Graduate School for Integrative Science and Engineering</wicri:noRegion></affiliation></author><author><name sortKey="Gehring, Adam J" sort="Gehring, Adam J" uniqKey="Gehring A" first="Adam J." last="Gehring">Adam J. Gehring</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Singapore Institute for Clinical Sciences, Technology and Research</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore Institute for Clinical Sciences, Technology and Research</wicri:noRegion></affiliation></author><author><name sortKey="Yee Joo Tan" sort="Yee Joo Tan" uniqKey="Yee Joo Tan" last="Yee Joo Tan">YEE JOO TAN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Technology and Research</s1><s3>SGP</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Technology and Research</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Agency for Science, Technology and Research</s1><s3>SGP</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Agency for Science, Technology and Research</wicri:noRegion></affiliation></author><author><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Singapore Institute for Clinical Sciences, Technology and Research</s1><s3>SGP</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore Institute for Clinical Sciences, Technology and Research</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Medicine</s1><s2>Singapore</s2><s3>SGP</s3><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Department of Medicine</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Singapore General Hospital and Program of Emerging Viral Diseases, Duke-NUS</s1><s3>SGP</s3><sZ>9 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore General Hospital and Program of Emerging Viral Diseases, Duke-NUS</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigenic determinant</term><term>CD8 T lymphocyte</term><term>Coronavirus</term><term>Severe acute respiratory syndrome</term><term>T-Lymphocyte</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Lymphocyte T</term><term>Lymphocyte T CD8</term><term>Déterminant antigénique</term><term>Syndrome respiratoire aigu sévère</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<sup>+</sup> and CD8<sup>+</sup> T cells. A dominant memory CD8<sup>+</sup> T cell response against SARS-CoV nucleocaspid protein (NP; amino acids 216 to 225) was then defined in SARS-recovered individuals carrying HLA-B<sup>*</sup>40:01, a HLA-B molecule present in approximately one-quarter of subjects of Asian ethnicities. To reconstitute such a CD8<sup>+</sup> T cell response, we isolated the alpha and beta T cell receptors of the HLA-B<sup>*</sup>40:01-restricted SARS-specific CD8<sup>+</sup> T cells. Using T cell receptor gene transfer, we generated SARS-specific redirected T cells from the lymphocytes of normal individuals. These engineered CD8<sup>+</sup> T cells displayed avidity and functionality similar to that of natural SARS-specific memory CD8<sup>+</sup> 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><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Janice Oh, Hsueh Ling" sort="Janice Oh, Hsueh Ling" uniqKey="Janice Oh H" first="Hsueh-Ling" last="Janice Oh">Hsueh-Ling Janice Oh</name></noRegion><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name><name sortKey="Bertoletti, Antonio" sort="Bertoletti, Antonio" uniqKey="Bertoletti A" first="Antonio" last="Bertoletti">Antonio Bertoletti</name><name sortKey="Chia, Adeline" sort="Chia, Adeline" uniqKey="Chia A" first="Adeline" last="Chia">Adeline Chia</name><name sortKey="Cynthia Xin Lei Chang" sort="Cynthia Xin Lei Chang" uniqKey="Cynthia Xin Lei Chang" last="Cynthia Xin Lei Chang">CYNTHIA XIN LEI CHANG</name><name sortKey="Cynthia Xin Lei Chang" sort="Cynthia Xin Lei Chang" uniqKey="Cynthia Xin Lei Chang" last="Cynthia Xin Lei Chang">CYNTHIA XIN LEI CHANG</name><name sortKey="Cynthia Xin Lei Chang" sort="Cynthia Xin Lei Chang" uniqKey="Cynthia Xin Lei Chang" last="Cynthia Xin Lei Chang">CYNTHIA XIN LEI CHANG</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="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M." last="Grotenbreg">Gijsbert M. Grotenbreg</name><name sortKey="Grotenbreg, Gijsbert M" sort="Grotenbreg, Gijsbert M" uniqKey="Grotenbreg G" first="Gijsbert M." last="Grotenbreg">Gijsbert M. Grotenbreg</name><name sortKey="Hoe Nam Leong" sort="Hoe Nam Leong" uniqKey="Hoe Nam Leong" last="Hoe Nam Leong">HOE NAM LEONG</name><name sortKey="Khoon Lin Ling" sort="Khoon Lin Ling" uniqKey="Khoon Lin Ling" last="Khoon Lin Ling">KHOON LIN LING</name><name sortKey="Yee Joo Tan" sort="Yee Joo Tan" uniqKey="Yee Joo Tan" last="Yee Joo Tan">YEE JOO TAN</name><name sortKey="Yee Joo Tan" sort="Yee Joo Tan" uniqKey="Yee Joo Tan" last="Yee Joo Tan">YEE JOO TAN</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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