Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A* 2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein
Identifieur interne : 002930 ( Main/Exploration ); précédent : 002929; suivant : 002931Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A* 2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein
Auteurs : JUN LIU [République populaire de Chine] ; PENG WU [République populaire de Chine] ; FENG GAO [République populaire de Chine] ; JIANXUN QI [République populaire de Chine] ; Ai Kawana-Tachikawa [Japon] ; JING XIE [République populaire de Chine] ; Christopher J. Vavricka [République populaire de Chine] ; Aikichi Iwamoto [Japon] ; TAISHENG LI [République populaire de Chine] ; George F. Gao [République populaire de Chine]Source :
- Journal of virology [ 0022-538X ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of in vitro studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β2-microglobulin (β2m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A<sup>*</sup> 2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein</title><author><name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>College of Life Sciences, Graduate University, Chinese Academy of Sciences</s1><s2>Beijing 100049</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Peng Wu" sort="Peng Wu" uniqKey="Peng Wu" last="Peng Wu">PENG WU</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Feng Gao" sort="Feng Gao" uniqKey="Feng Gao" last="Feng Gao">FENG GAO</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Biophysics (IBP), Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>3 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Kawana Tachikawa, Ai" sort="Kawana Tachikawa, Ai" uniqKey="Kawana Tachikawa A" first="Ai" last="Kawana-Tachikawa">Ai Kawana-Tachikawa</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Jing Xie" sort="Jing Xie" uniqKey="Jing Xie" last="Jing Xie">JING XIE</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Vavricka, Christopher J" sort="Vavricka, Christopher J" uniqKey="Vavricka C" first="Christopher J." last="Vavricka">Christopher J. Vavricka</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Institute of Medical Science, University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Taisheng Li" sort="Taisheng Li" uniqKey="Taisheng Li" last="Taisheng Li">TAISHENG LI</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>College of Life Sciences, Graduate University, Chinese Academy of Sciences</s1><s2>Beijing 100049</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Beijing Institutes of Life Science, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0511488</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0511488 INIST</idno><idno type="RBID">Pascal:10-0511488</idno><idno type="wicri:Area/PascalFrancis/Corpus">000127</idno><idno type="wicri:Area/PascalFrancis/Curation">000861</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000139</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000139</idno><idno type="wicri:doubleKey">0022-538X:2010:Jun Liu:novel:immunodominant:peptide</idno><idno type="wicri:Area/Main/Merge">002971</idno><idno type="wicri:Area/Main/Curation">002930</idno><idno type="wicri:Area/Main/Exploration">002930</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A<sup>*</sup> 2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein</title><author><name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>College of Life Sciences, Graduate University, Chinese Academy of Sciences</s1><s2>Beijing 100049</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Peng Wu" sort="Peng Wu" uniqKey="Peng Wu" last="Peng Wu">PENG WU</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Feng Gao" sort="Feng Gao" uniqKey="Feng Gao" last="Feng Gao">FENG GAO</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Biophysics (IBP), Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>3 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Kawana Tachikawa, Ai" sort="Kawana Tachikawa, Ai" uniqKey="Kawana Tachikawa A" first="Ai" last="Kawana-Tachikawa">Ai Kawana-Tachikawa</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Jing Xie" sort="Jing Xie" uniqKey="Jing Xie" last="Jing Xie">JING XIE</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Vavricka, Christopher J" sort="Vavricka, Christopher J" uniqKey="Vavricka C" first="Christopher J." last="Vavricka">Christopher J. Vavricka</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Institute of Medical Science, University of Tokyo</s1><s2>Minato-ku, 108-8639 Tokyo</s2><s3>JPN</s3><sZ>8 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName><placeName><settlement type="city">Tokyo</settlement><region type="province">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Taisheng Li" sort="Taisheng Li" uniqKey="Taisheng Li" last="Taisheng Li">TAISHENG LI</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences</s1><s2>Beijing 100730</s2><s3>CHN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>College of Life Sciences, Graduate University, Chinese Academy of Sciences</s1><s2>Beijing 100049</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Beijing Institutes of Life Science, Chinese Academy of Sciences</s1><s2>Beijing 100101</s2><s3>CHN</s3><sZ>10 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></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="2010">2010</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>Coronavirus</term><term>Cytotoxic T lymphocyte</term><term>Cytotoxicity</term><term>Histocompatibility restriction</term><term>Immunodominance</term><term>Nucleocapsid</term><term>Peptides</term><term>Protein</term><term>Severe acute respiratory syndrome</term><term>T-Lymphocyte</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Immunodominance</term><term>Peptide</term><term>Restriction histocompatibilité</term><term>Cytotoxicité</term><term>Lymphocyte T cytotoxique</term><term>Lymphocyte T</term><term>Déterminant antigénique</term><term>Nucléocapside</term><term>Syndrome respiratoire aigu sévère</term><term>Protéine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A<sup>*</sup>2402 was identified by a series of in vitro studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A<sup>*</sup>2402 heavy chain and β<sub>2</sub>-microglobulin (β<sub>2</sub>m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A<sup>*</sup>2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.</div></front></TEI><affiliations><list><country><li>Japon</li><li>République populaire de Chine</li></country><region><li>Région de Kantō</li></region><settlement><li>Pékin</li><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name></noRegion><name sortKey="Feng Gao" sort="Feng Gao" uniqKey="Feng Gao" last="Feng Gao">FENG GAO</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name><name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name><name sortKey="Jing Xie" sort="Jing Xie" uniqKey="Jing Xie" last="Jing Xie">JING XIE</name><name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name><name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name><name sortKey="Peng Wu" sort="Peng Wu" uniqKey="Peng Wu" last="Peng Wu">PENG WU</name><name sortKey="Taisheng Li" sort="Taisheng Li" uniqKey="Taisheng Li" last="Taisheng Li">TAISHENG LI</name><name sortKey="Vavricka, Christopher J" sort="Vavricka, Christopher J" uniqKey="Vavricka C" first="Christopher J." last="Vavricka">Christopher J. Vavricka</name></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Kawana Tachikawa, Ai" sort="Kawana Tachikawa, Ai" uniqKey="Kawana Tachikawa A" first="Ai" last="Kawana-Tachikawa">Ai Kawana-Tachikawa</name></region><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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