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 : 002524 ( Main/Merge ); précédent : 002523; suivant : 002525Novel 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 ; Peng Wu ; Feng Gao ; Jianxun Qi ; Ai Kawana-Tachikawa ; Jing Xie ; Christopher J. Vavricka ; Aikichi Iwamoto ; Taisheng Li ; George F. GaoSource :
- Journal of Virology [ 0022-538X ] ; 2010.
Descripteurs français
- KwdFr :
- Adulte, Agranulocytes (), Agranulocytes (immunologie), Agranulocytes (virologie), Antigènes HLA-A (), Antigènes HLA-A (génétique), Antigènes HLA-A (immunologie), Cartographie épitopique (), Cellules cultivées, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T (), Déterminants antigéniques des lymphocytes T (génétique), Déterminants antigéniques des lymphocytes T (immunologie), Femelle, Fragments peptidiques (), Fragments peptidiques (génétique), Fragments peptidiques (immunologie), Humains, Liaison hydrogène, Lignée cellulaire, Lymphocytes T cytotoxiques (), Lymphocytes T cytotoxiques (immunologie), Modèles moléculaires, Mâle, Pliage des protéines, Protéines nucléocapside (), Protéines nucléocapside (génétique), Protéines nucléocapside (immunologie), Sites de fixation, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Séquence d'acides aminés, Virus du SRAS (), Virus du SRAS (génétique), Virus du SRAS (immunologie).
- MESH :
- génétique : Antigènes HLA-A, Déterminants antigéniques des lymphocytes T, Fragments peptidiques, Protéines nucléocapside, Virus du SRAS.
- immunologie : Agranulocytes, Antigènes HLA-A, Déterminants antigéniques des lymphocytes T, Fragments peptidiques, Lymphocytes T cytotoxiques, Protéines nucléocapside, Syndrome respiratoire aigu sévère, Virus du SRAS.
- virologie : Agranulocytes, Syndrome respiratoire aigu sévère.
- Adulte, Agranulocytes, Antigènes HLA-A, Cartographie épitopique, Cellules cultivées, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T, Femelle, Fragments peptidiques, Humains, Liaison hydrogène, Lignée cellulaire, Lymphocytes T cytotoxiques, Modèles moléculaires, Mâle, Pliage des protéines, Protéines nucléocapside, Sites de fixation, Séquence d'acides aminés, Virus du SRAS.
English descriptors
- KwdEn :
- Adult, Amino Acid Sequence, Binding Sites, Cell Line, Cells, Cultured, Epitope Mapping (methods), Epitopes, T-Lymphocyte (chemistry), Epitopes, T-Lymphocyte (genetics), Epitopes, T-Lymphocyte (immunology), Female, HLA-A Antigens (chemistry), HLA-A Antigens (genetics), HLA-A Antigens (immunology), Humans, Hydrogen Bonding, Leukocytes, Mononuclear (chemistry), Leukocytes, Mononuclear (immunology), Leukocytes, Mononuclear (virology), Male, Models, Molecular, Molecular Sequence Data, Nucleocapsid Proteins (chemistry), Nucleocapsid Proteins (genetics), Nucleocapsid Proteins (immunology), Peptide Fragments (chemistry), Peptide Fragments (genetics), Peptide Fragments (immunology), Protein Folding, SARS Virus (chemistry), SARS Virus (genetics), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), T-Lymphocytes, Cytotoxic (chemistry), T-Lymphocytes, Cytotoxic (immunology).
- MESH :
- chemical , chemistry : Epitopes, T-Lymphocyte, HLA-A Antigens, Nucleocapsid Proteins, Peptide Fragments.
- chemical , genetics : Epitopes, T-Lymphocyte, HLA-A Antigens, Nucleocapsid Proteins, Peptide Fragments.
- chemical , immunology : Epitopes, T-Lymphocyte, HLA-A Antigens, Nucleocapsid Proteins, Peptide Fragments.
- chemistry : Leukocytes, Mononuclear, SARS Virus, T-Lymphocytes, Cytotoxic.
- genetics : SARS Virus.
- immunology : Leukocytes, Mononuclear, SARS Virus, Severe Acute Respiratory Syndrome, T-Lymphocytes, Cytotoxic.
- methods : Epitope Mapping.
- virology : Leukocytes, Mononuclear, Severe Acute Respiratory Syndrome.
- Adult, Amino Acid Sequence, Binding Sites, Cell Line, Cells, Cultured, Female, Humans, Hydrogen Bonding, Male, Models, Molecular, Molecular Sequence Data, Protein Folding.
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
Url:
DOI: 10.1128/JVI.01464-10
PubMed: 20844028
PubMed Central: 2977860
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PMC:2977860Le document en format XML
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Amino Acid Sequence</term>
<term>Binding Sites</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Epitope Mapping (methods)</term>
<term>Epitopes, T-Lymphocyte (chemistry)</term>
<term>Epitopes, T-Lymphocyte (genetics)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Female</term>
<term>HLA-A Antigens (chemistry)</term>
<term>HLA-A Antigens (genetics)</term>
<term>HLA-A Antigens (immunology)</term>
<term>Humans</term>
<term>Hydrogen Bonding</term>
<term>Leukocytes, Mononuclear (chemistry)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Leukocytes, Mononuclear (virology)</term>
<term>Male</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Nucleocapsid Proteins (chemistry)</term>
<term>Nucleocapsid Proteins (genetics)</term>
<term>Nucleocapsid Proteins (immunology)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Protein Folding</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>T-Lymphocytes, Cytotoxic (chemistry)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Agranulocytes ()</term>
<term>Agranulocytes (immunologie)</term>
<term>Agranulocytes (virologie)</term>
<term>Antigènes HLA-A ()</term>
<term>Antigènes HLA-A (génétique)</term>
<term>Antigènes HLA-A (immunologie)</term>
<term>Cartographie épitopique ()</term>
<term>Cellules cultivées</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T ()</term>
<term>Déterminants antigéniques des lymphocytes T (génétique)</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Femelle</term>
<term>Fragments peptidiques ()</term>
<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Humains</term>
<term>Liaison hydrogène</term>
<term>Lignée cellulaire</term>
<term>Lymphocytes T cytotoxiques ()</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Modèles moléculaires</term>
<term>Mâle</term>
<term>Pliage des protéines</term>
<term>Protéines nucléocapside ()</term>
<term>Protéines nucléocapside (génétique)</term>
<term>Protéines nucléocapside (immunologie)</term>
<term>Sites de fixation</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Nucleocapsid Proteins</term>
<term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Nucleocapsid Proteins</term>
<term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes, T-Lymphocyte</term>
<term>HLA-A Antigens</term>
<term>Nucleocapsid Proteins</term>
<term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Leukocytes, Mononuclear</term>
<term>SARS Virus</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes HLA-A</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Protéines nucléocapside</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Agranulocytes</term>
<term>Antigènes HLA-A</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Fragments peptidiques</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Protéines nucléocapside</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Leukocytes, Mononuclear</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Epitope Mapping</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Agranulocytes</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Leukocytes, Mononuclear</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Amino Acid Sequence</term>
<term>Binding Sites</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Female</term>
<term>Humans</term>
<term>Hydrogen Bonding</term>
<term>Male</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Protein Folding</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Agranulocytes</term>
<term>Antigènes HLA-A</term>
<term>Cartographie épitopique</term>
<term>Cellules cultivées</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Femelle</term>
<term>Fragments peptidiques</term>
<term>Humains</term>
<term>Liaison hydrogène</term>
<term>Lignée cellulaire</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Modèles moléculaires</term>
<term>Mâle</term>
<term>Pliage des protéines</term>
<term>Protéines nucléocapside</term>
<term>Sites de fixation</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>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 <italic>in vitro</italic>
studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*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*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.</p>
</div>
</front>
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