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Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein.

Identifieur interne : 005720 ( Main/Merge ); précédent : 005719; suivant : 005721

Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein.

Auteurs : Baomei Wang [République populaire de Chine] ; Huabiao Chen ; Xiaodong Jiang ; Minghui Zhang ; Tao Wan ; Nan Li ; Xiangyang Zhou ; Yanfeng Wu ; Feng Yang ; Yizhi Yu ; Xiaoning Wang ; Ruifu Yang ; Xuetao Cao

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RBID : pubmed:15016646

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Abstract

A novel coronavirus, severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/K(b) transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) harvested from healthy HLA-A2.1(+) donors. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs), which specifically released interferon-gamma (IFN-gamma) upon stimulation with SSp-1-pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1-specific CTLs also lysed major histocompatibility complex (MHC)-matched tumor cell lines engineered to express S proteins. HLA-A*0201-SSp-1 tetramer staining revealed the presence of significant populations of SSp-1-specific CTLs in SSp-1-induced CD8(+) T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.

DOI: 10.1182/blood-2003-11-4072
PubMed: 15016646

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Le document en format XML

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<name sortKey="Yang, Feng" sort="Yang, Feng" uniqKey="Yang F" first="Feng" last="Yang">Feng Yang</name>
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<name sortKey="Wang, Baomei" sort="Wang, Baomei" uniqKey="Wang B" first="Baomei" last="Wang">Baomei Wang</name>
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<nlm:affiliation>Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
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<wicri:noRegion>Shanghai</wicri:noRegion>
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<name sortKey="Chen, Huabiao" sort="Chen, Huabiao" uniqKey="Chen H" first="Huabiao" last="Chen">Huabiao Chen</name>
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<name sortKey="Jiang, Xiaodong" sort="Jiang, Xiaodong" uniqKey="Jiang X" first="Xiaodong" last="Jiang">Xiaodong Jiang</name>
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<name sortKey="Zhang, Minghui" sort="Zhang, Minghui" uniqKey="Zhang M" first="Minghui" last="Zhang">Minghui Zhang</name>
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<name sortKey="Wan, Tao" sort="Wan, Tao" uniqKey="Wan T" first="Tao" last="Wan">Tao Wan</name>
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<name sortKey="Li, Nan" sort="Li, Nan" uniqKey="Li N" first="Nan" last="Li">Nan Li</name>
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<name sortKey="Zhou, Xiangyang" sort="Zhou, Xiangyang" uniqKey="Zhou X" first="Xiangyang" last="Zhou">Xiangyang Zhou</name>
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<name sortKey="Wu, Yanfeng" sort="Wu, Yanfeng" uniqKey="Wu Y" first="Yanfeng" last="Wu">Yanfeng Wu</name>
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<name sortKey="Yang, Feng" sort="Yang, Feng" uniqKey="Yang F" first="Feng" last="Yang">Feng Yang</name>
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<name sortKey="Yu, Yizhi" sort="Yu, Yizhi" uniqKey="Yu Y" first="Yizhi" last="Yu">Yizhi Yu</name>
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<name sortKey="Wang, Xiaoning" sort="Wang, Xiaoning" uniqKey="Wang X" first="Xiaoning" last="Wang">Xiaoning Wang</name>
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<name sortKey="Yang, Ruifu" sort="Yang, Ruifu" uniqKey="Yang R" first="Ruifu" last="Yang">Ruifu Yang</name>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Cell Line</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>HLA-A Antigens (chemistry)</term>
<term>HLA-A Antigens (genetics)</term>
<term>HLA-A Antigens (immunology)</term>
<term>HLA-A Antigens (metabolism)</term>
<term>HLA-A2 Antigen</term>
<term>Humans</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Peptide Fragments (metabolism)</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (immunology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Spleen (cytology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (metabolism)</term>
<term>Transduction, Genetic</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Structural Proteins (genetics)</term>
<term>Viral Structural Proteins (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Antigène HLA-A2</term>
<term>Antigènes HLA-A ()</term>
<term>Antigènes HLA-A (génétique)</term>
<term>Antigènes HLA-A (immunologie)</term>
<term>Antigènes HLA-A (métabolisme)</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Fragments peptidiques (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Lignée cellulaire</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Lymphocytes T cytotoxiques (métabolisme)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines virales structurales (génétique)</term>
<term>Protéines virales structurales (immunologie)</term>
<term>Rate (cytologie)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence d'acides aminés</term>
<term>Transduction génétique</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Interferon-gamma</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>HLA-A Antigens</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>HLA-A Antigens</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Viral Envelope Proteins</term>
<term>Viral Structural Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Viral Envelope Proteins</term>
<term>Viral Structural Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Interféron gamma</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Rate</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Antigènes HLA-A</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines virales structurales</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Antigènes HLA-A</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines virales structurales</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>CD8-Positive T-Lymphocytes</term>
<term>SARS Virus</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>HLA-A Antigens</term>
<term>Peptide Fragments</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Antigènes HLA-A</term>
<term>Fragments peptidiques</term>
<term>Lymphocytes T cytotoxiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Line</term>
<term>HLA-A2 Antigen</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transduction, Genetic</term>
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<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Antigène HLA-A2</term>
<term>Antigènes HLA-A</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence d'acides aminés</term>
<term>Transduction génétique</term>
<term>Virus du SRAS</term>
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<front>
<div type="abstract" xml:lang="en">A novel coronavirus, severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/K(b) transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) harvested from healthy HLA-A2.1(+) donors. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs), which specifically released interferon-gamma (IFN-gamma) upon stimulation with SSp-1-pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1-specific CTLs also lysed major histocompatibility complex (MHC)-matched tumor cell lines engineered to express S proteins. HLA-A*0201-SSp-1 tetramer staining revealed the presence of significant populations of SSp-1-specific CTLs in SSp-1-induced CD8(+) T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.</div>
</front>
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