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Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes.

Identifieur interne : 002011 ( PubMed/Checkpoint ); précédent : 002010; suivant : 002012

Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes.

Auteurs : Minghai Zhou ; Dongping Xu ; Xiaojuan Li ; Hongtao Li ; Ming Shan ; Jiaren Tang ; Min Wang ; Fu-Sheng Wang ; Xiaodong Zhu ; Hua Tao ; Wei He ; Po Tien ; George F. Gao

Source :

RBID : pubmed:16887973

Descripteurs français

English descriptors

Abstract

Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.

DOI: 10.4049/jimmunol.177.4.2138
PubMed: 16887973


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<term>Epitopes, T-Lymphocyte (isolation & purification)</term>
<term>Epitopes, T-Lymphocyte (metabolism)</term>
<term>HLA-A Antigens (biosynthesis)</term>
<term>HLA-A Antigens (metabolism)</term>
<term>HLA-A2 Antigen</term>
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<term>Interferon-gamma (metabolism)</term>
<term>Intracellular Fluid (immunology)</term>
<term>Intracellular Fluid (metabolism)</term>
<term>Intracellular Fluid (virology)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Leukocytes, Mononuclear (virology)</term>
<term>Lymphocyte Activation (immunology)</term>
<term>Membrane Glycoproteins (administration & dosage)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (isolation & purification)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Nucleocapsid Proteins (immunology)</term>
<term>Nucleocapsid Proteins (isolation & purification)</term>
<term>Nucleocapsid Proteins (metabolism)</term>
<term>Peptide Fragments (administration & dosage)</term>
<term>Peptide Fragments (immunology)</term>
<term>Peptide Fragments (isolation & purification)</term>
<term>Peptide Fragments (metabolism)</term>
<term>Protein Binding (immunology)</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (isolation & purification)</term>
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<term>Membrane Glycoproteins</term>
<term>Nucleocapsid Proteins</term>
<term>Peptide Fragments</term>
<term>Vaccines, DNA</term>
<term>Viral Envelope Proteins</term>
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<term>Vaccins à ADN</term>
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<term>Agranulocytes</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Liaison aux protéines</term>
<term>Liquide intracellulaire</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines nucléocapside</term>
<term>Vaccins à ADN</term>
<term>Virus du SRAS</term>
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<term>SARS Virus</term>
<term>T-Lymphocytes, Cytotoxic</term>
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<term>SARS Virus</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines nucléocapside</term>
<term>Virus du SRAS</term>
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<term>Intracellular Fluid</term>
<term>SARS Virus</term>
<term>T-Lymphocytes, Cytotoxic</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>Liquide intracellulaire</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines nucléocapside</term>
<term>Virus du SRAS</term>
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<term>Agranulocytes</term>
<term>Liquide intracellulaire</term>
<term>Lymphocytes T cytotoxiques</term>
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<term>T-Lymphocytes, Cytotoxic</term>
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<term>Cells, Cultured</term>
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<term>Antigène HLA-A2</term>
<term>Cellules cultivées</term>
<term>Glycoprotéine de spicule des coronavirus</term>
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<term>Souris</term>
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<front>
<div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.</div>
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<MeshHeading>
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<MeshHeading>
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<name sortKey="He, Wei" sort="He, Wei" uniqKey="He W" first="Wei" last="He">Wei He</name>
<name sortKey="Li, Hongtao" sort="Li, Hongtao" uniqKey="Li H" first="Hongtao" last="Li">Hongtao Li</name>
<name sortKey="Li, Xiaojuan" sort="Li, Xiaojuan" uniqKey="Li X" first="Xiaojuan" last="Li">Xiaojuan Li</name>
<name sortKey="Shan, Ming" sort="Shan, Ming" uniqKey="Shan M" first="Ming" last="Shan">Ming Shan</name>
<name sortKey="Tang, Jiaren" sort="Tang, Jiaren" uniqKey="Tang J" first="Jiaren" last="Tang">Jiaren Tang</name>
<name sortKey="Tao, Hua" sort="Tao, Hua" uniqKey="Tao H" first="Hua" last="Tao">Hua Tao</name>
<name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name>
<name sortKey="Wang, Fu Sheng" sort="Wang, Fu Sheng" uniqKey="Wang F" first="Fu-Sheng" last="Wang">Fu-Sheng Wang</name>
<name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name>
<name sortKey="Xu, Dongping" sort="Xu, Dongping" uniqKey="Xu D" first="Dongping" last="Xu">Dongping Xu</name>
<name sortKey="Zhou, Minghai" sort="Zhou, Minghai" uniqKey="Zhou M" first="Minghai" last="Zhou">Minghai Zhou</name>
<name sortKey="Zhu, Xiaodong" sort="Zhu, Xiaodong" uniqKey="Zhu X" first="Xiaodong" last="Zhu">Xiaodong Zhu</name>
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