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Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV

Identifieur interne : 002B00 ( Main/Exploration ); précédent : 002A99; suivant : 002B01

Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV

Auteurs : Yanbo Lv ; Zhihua Ruan ; Li Wang ; Bing Ni ; Yuzhang Wu

Source :

RBID : PMC:2792222

Descripteurs français

English descriptors

Abstract

Background

The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein.

Results

First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S958-966, VLNDILSRL) induced specific CTLs both ex vivo in PBLs of healthy HLA-A2+ donors and in HLA-A2.1/Kb transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates.

Conclusion

These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2172-10-61) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1186/1471-2172-10-61
PubMed: 19958537
PubMed Central: 2792222


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Cell Line</term>
<term>Conserved Sequence</term>
<term>Coronavirus (immunology)</term>
<term>Cytotoxicity, Immunologic</term>
<term>Epitope Mapping</term>
<term>Epitopes, T-Lymphocyte (genetics)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Epitopes, T-Lymphocyte (metabolism)</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>Immunization</term>
<term>Interferon-gamma (metabolism)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Peptide Fragments (metabolism)</term>
<term>Protein Binding</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (metabolism)</term>
<term>T-Lymphocytes, Cytotoxic (pathology)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
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<term>Animaux</term>
<term>Antigène HLA-A2</term>
<term>Antigènes HLA-A (génétique)</term>
<term>Antigènes HLA-A (immunologie)</term>
<term>Antigènes HLA-A (métabolisme)</term>
<term>Cartographie épitopique</term>
<term>Coronavirus (immunologie)</term>
<term>Cytotoxicité immunologique</term>
<term>Déterminants antigéniques des lymphocytes T (génétique)</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Déterminants antigéniques des lymphocytes T (métabolisme)</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>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Immunisation</term>
<term>Interféron gamma (métabolisme)</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Lymphocytes T cytotoxiques (anatomopathologie)</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 de l'enveloppe virale (métabolisme)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Séquence conservée</term>
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<term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Viral Envelope Proteins</term>
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<term>Lymphocytes T cytotoxiques</term>
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<term>Antigènes HLA-A</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
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<term>Antigènes HLA-A</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines de l'enveloppe virale</term>
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<term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>T-Lymphocytes, Cytotoxic</term>
<term>Viral Envelope Proteins</term>
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<term>HLA-A Antigens</term>
<term>Interferon-gamma</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>T-Lymphocytes, Cytotoxic</term>
<term>Viral Envelope Proteins</term>
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<term>Antigènes HLA-A</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Interféron gamma</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines de l'enveloppe virale</term>
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<term>Animals</term>
<term>Cell Line</term>
<term>Conserved Sequence</term>
<term>Cytotoxicity, Immunologic</term>
<term>Epitope Mapping</term>
<term>HLA-A2 Antigen</term>
<term>Humans</term>
<term>Immunization</term>
<term>Mice</term>
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<term>Immunisation</term>
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<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein.</p>
</sec>
<sec>
<title>Results</title>
<p>First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S
<sub>958-966</sub>
, VLNDILSRL) induced specific CTLs both
<italic>ex vivo</italic>
in PBLs of healthy HLA-A2
<sup>+</sup>
donors and in HLA-A2.1/K
<sup>b</sup>
transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.</p>
</sec>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/1471-2172-10-61) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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