The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as a Dominant Immunogen Revealed by a Clustering Region of Novel Functionally and Structurally Defined Cytotoxic T-Lymphocyte Epitopes
Identifieur interne : 002609 ( Main/Exploration ); précédent : 002608; suivant : 002610The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as a Dominant Immunogen Revealed by a Clustering Region of Novel Functionally and Structurally Defined Cytotoxic T-Lymphocyte Epitopes
Auteurs : Jun Liu ; Yeping Sun ; Jianxun Qi ; Fuliang Chu ; Hao Wu ; Feng Gao ; Taisheng Li ; Jinghua Yan ; George F. Gao [République populaire de Chine]Source :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Antigène HLA-A2, Antigènes HLA-A (métabolisme), Déterminants antigéniques des lymphocytes T (immunologie), Humains, Immunité cellulaire, Lymphocytes T CD8+ (immunologie), Lymphocytes T cytotoxiques (immunologie), Modèles moléculaires, Protéines de la matrice virale (), Protéines de la matrice virale (immunologie), Protéines de transport, Souris, Souris de lignée C57BL, Souris transgéniques, Structure quaternaire des protéines, Syndrome respiratoire aigu sévère (immunologie), Vaccins antiviraux (immunologie), Vaccins à ADN (immunologie), Virus du SRAS (immunologie).
- MESH :
- immunologie : Déterminants antigéniques des lymphocytes T, Lymphocytes T CD8+, Lymphocytes T cytotoxiques, Protéines de la matrice virale, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Vaccins à ADN, Virus du SRAS.
- métabolisme : Antigènes HLA-A.
- Animaux, Antigène HLA-A2, Humains, Immunité cellulaire, Modèles moléculaires, Protéines de la matrice virale, Protéines de transport, Souris, Souris de lignée C57BL, Souris transgéniques, Structure quaternaire des protéines.
English descriptors
- KwdEn :
- Animals, CD8-Positive T-Lymphocytes (immunology), Carrier Proteins, Epitopes, T-Lymphocyte (immunology), HLA-A Antigens (metabolism), HLA-A2 Antigen, Humans, Immunity, Cellular, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Molecular, Protein Structure, Quaternary, SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), T-Lymphocytes, Cytotoxic (immunology), Vaccines, DNA (immunology), Viral Matrix Proteins (chemistry), Viral Matrix Proteins (immunology), Viral Vaccines (immunology).
- MESH :
- chemical , chemistry : Viral Matrix Proteins.
- chemical , immunology : Epitopes, T-Lymphocyte, Vaccines, DNA, Viral Matrix Proteins, Viral Vaccines.
- chemical , metabolism : HLA-A Antigens.
- chemical : Carrier Proteins, HLA-A2 Antigen.
- immunology : CD8-Positive T-Lymphocytes, SARS Virus, Severe Acute Respiratory Syndrome, T-Lymphocytes, Cytotoxic.
- Animals, Humans, Immunity, Cellular, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Molecular, Protein Structure, Quaternary.
Abstract
Background. Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV. The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive. Methods. In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/Kb transgenic mice and human peripheral blood mononuclear cells (PBMCs). Results. A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3. Conclusions. The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.
Url:
DOI: 10.1086/656315
Affiliations:
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Gao</name><affiliation></affiliation><affiliation></affiliation><affiliation></affiliation><affiliation wicri:level="3"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Institutes of Life Science, CAS, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">République populaire de Chine</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>University of Chicago Press</publisher><date type="published">2010</date><biblScope unit="vol">202</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1171">1171</biblScope><biblScope unit="page" to="1180">1180</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Carrier Proteins</term><term>Epitopes, T-Lymphocyte (immunology)</term><term>HLA-A Antigens (metabolism)</term><term>HLA-A2 Antigen</term><term>Humans</term><term>Immunity, Cellular</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Models, Molecular</term><term>Protein Structure, Quaternary</term><term>SARS Virus (immunology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>T-Lymphocytes, Cytotoxic (immunology)</term><term>Vaccines, DNA (immunology)</term><term>Viral Matrix Proteins (chemistry)</term><term>Viral Matrix Proteins (immunology)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigène HLA-A2</term><term>Antigènes HLA-A (métabolisme)</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Humains</term><term>Immunité cellulaire</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Lymphocytes T cytotoxiques (immunologie)</term><term>Modèles moléculaires</term><term>Protéines de la matrice virale ()</term><term>Protéines de la matrice virale (immunologie)</term><term>Protéines de transport</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term><term>Structure quaternaire des protéines</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Vaccins à ADN (immunologie)</term><term>Virus du SRAS (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Vaccines, DNA</term><term>Viral Matrix Proteins</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HLA-A Antigens</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Carrier Proteins</term><term>HLA-A2 Antigen</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term><term>Lymphocytes T CD8+</term><term>Lymphocytes T cytotoxiques</term><term>Protéines de la matrice virale</term><term>Syndrome respiratoire aigu sévère</term><term>Vaccins antiviraux</term><term>Vaccins à ADN</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>Severe Acute Respiratory Syndrome</term><term>T-Lymphocytes, Cytotoxic</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes HLA-A</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Immunity, Cellular</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Models, Molecular</term><term>Protein Structure, Quaternary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antigène HLA-A2</term><term>Humains</term><term>Immunité cellulaire</term><term>Modèles moléculaires</term><term>Protéines de la matrice virale</term><term>Protéines de transport</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term><term>Structure quaternaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Background. Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV. The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive. Methods. In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/Kb transgenic mice and human peripheral blood mononuclear cells (PBMCs). Results. A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3. Conclusions. The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><noCountry><name sortKey="Chu, Fuliang" sort="Chu, Fuliang" uniqKey="Chu F" first="Fuliang" last="Chu">Fuliang Chu</name><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name><name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name><name sortKey="Sun, Yeping" sort="Sun, Yeping" uniqKey="Sun Y" first="Yeping" last="Sun">Yeping Sun</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name></noRegion><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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