Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells.
Identifieur interne : 002F02 ( Main/Exploration ); précédent : 002F01; suivant : 002F03Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells.
Auteurs : Yufei Wang [Royaume-Uni] ; Trevor Whittall ; Edward Mcgowan ; Justine Younson ; Charles Kelly ; Lesley A. Bergmeier ; Mahavir Singh ; Thomas LehnerSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2005.
Descripteurs français
- KwdFr :
- Cellules dendritiques (cytologie), Cellules dendritiques (immunologie), Cytokines (biosynthèse), Différenciation cellulaire, Données de séquences moléculaires, Fragments peptidiques (génétique), Fragments peptidiques (immunologie), Fragments peptidiques (métabolisme), Humains, Ligand de CD40 (métabolisme), Lignée cellulaire, Monocytes (immunologie), Protéines Escherichia coli (génétique), Protéines Escherichia coli (immunologie), Protéines Escherichia coli (métabolisme), Protéines du choc thermique HSP70 (génétique), Protéines du choc thermique HSP70 (immunologie), Protéines du choc thermique HSP70 (métabolisme), Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Protéines recombinantes (métabolisme), Sites de fixation (génétique), Structure tertiaire des protéines, Substitution d'acide aminé, Séquence d'acides aminés, Techniques in vitro, p38 Mitogen-Activated Protein Kinases (métabolisme), Épitopes (génétique).
- MESH :
- biosynthèse : Cytokines.
- cytologie : Cellules dendritiques.
- génétique : Fragments peptidiques, Protéines Escherichia coli, Protéines du choc thermique HSP70, Protéines recombinantes, Sites de fixation, Épitopes.
- immunologie : Cellules dendritiques, Fragments peptidiques, Monocytes, Protéines Escherichia coli, Protéines du choc thermique HSP70, Protéines recombinantes.
- métabolisme : Fragments peptidiques, Ligand de CD40, Protéines Escherichia coli, Protéines du choc thermique HSP70, Protéines recombinantes, p38 Mitogen-Activated Protein Kinases.
- Différenciation cellulaire, Données de séquences moléculaires, Humains, Lignée cellulaire, Structure tertiaire des protéines, Substitution d'acide aminé, Séquence d'acides aminés, Techniques in vitro.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Binding Sites (genetics), CD40 Ligand (metabolism), Cell Differentiation, Cell Line, Cytokines (biosynthesis), Dendritic Cells (cytology), Dendritic Cells (immunology), Epitopes (genetics), Escherichia coli Proteins (genetics), Escherichia coli Proteins (immunology), Escherichia coli Proteins (metabolism), HSP70 Heat-Shock Proteins (genetics), HSP70 Heat-Shock Proteins (immunology), HSP70 Heat-Shock Proteins (metabolism), Humans, In Vitro Techniques, Molecular Sequence Data, Monocytes (immunology), Peptide Fragments (genetics), Peptide Fragments (immunology), Peptide Fragments (metabolism), Protein Structure, Tertiary, Recombinant Proteins (genetics), Recombinant Proteins (immunology), Recombinant Proteins (metabolism), p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , biosynthesis : Cytokines.
- chemical , genetics : Epitopes, Escherichia coli Proteins, HSP70 Heat-Shock Proteins, Peptide Fragments, Recombinant Proteins.
- chemical , immunology : Escherichia coli Proteins, HSP70 Heat-Shock Proteins, Peptide Fragments, Recombinant Proteins.
- chemical , metabolism : CD40 Ligand, Escherichia coli Proteins, HSP70 Heat-Shock Proteins, Peptide Fragments, Recombinant Proteins, p38 Mitogen-Activated Protein Kinases.
- cytology : Dendritic Cells.
- genetics : Binding Sites.
- immunology : Dendritic Cells, Monocytes.
- Amino Acid Sequence, Amino Acid Substitution, Cell Differentiation, Cell Line, Humans, In Vitro Techniques, Molecular Sequence Data, Protein Structure, Tertiary.
Abstract
The 70-kDa microbial heat shock protein (mHSP70) has a profound effect on the immune system, interacting with the CD40 receptor on DC and monocytes to produce cytokines and chemokines. The mHSP70 also induces maturation of dendritic cells (DC) and thus acts as an alternative ligand to CD40L on T cells. In this investigation, we have identified a cytokine-stimulating epitope (peptide 407-426), by activating DC with overlapping synthetic peptides (20-mers) derived from the sequence of mHSP70. This peptide also significantly enhances maturation of DC stimulated by mHSP70 or CD40L. The epitope is located at the base of the peptide-binding groove of HSP70 and has five critical residues. Furthermore, an inhibitory epitope (p457-496) was identified downstream from the peptide-binding groove that inhibits cytokine production and maturation of DC stimulated by HSP70 or CD40L. The p38 MAP kinase phosphorylation is critical in the alternative CD40-HSP70 pathway and is inhibited by p457-496 but enhanced by p407-426.
DOI: 10.4049/jimmunol.174.6.3306
PubMed: 15749862
Affiliations:
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Le document en format XML
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<term>Amino Acid Substitution</term>
<term>Binding Sites (genetics)</term>
<term>CD40 Ligand (metabolism)</term>
<term>Cell Differentiation</term>
<term>Cell Line</term>
<term>Cytokines (biosynthesis)</term>
<term>Dendritic Cells (cytology)</term>
<term>Dendritic Cells (immunology)</term>
<term>Epitopes (genetics)</term>
<term>Escherichia coli Proteins (genetics)</term>
<term>Escherichia coli Proteins (immunology)</term>
<term>Escherichia coli Proteins (metabolism)</term>
<term>HSP70 Heat-Shock Proteins (genetics)</term>
<term>HSP70 Heat-Shock Proteins (immunology)</term>
<term>HSP70 Heat-Shock Proteins (metabolism)</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Molecular Sequence Data</term>
<term>Monocytes (immunology)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Peptide Fragments (metabolism)</term>
<term>Protein Structure, Tertiary</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (immunology)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>p38 Mitogen-Activated Protein Kinases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules dendritiques (cytologie)</term>
<term>Cellules dendritiques (immunologie)</term>
<term>Cytokines (biosynthèse)</term>
<term>Différenciation cellulaire</term>
<term>Données de séquences moléculaires</term>
<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Fragments peptidiques (métabolisme)</term>
<term>Humains</term>
<term>Ligand de CD40 (métabolisme)</term>
<term>Lignée cellulaire</term>
<term>Monocytes (immunologie)</term>
<term>Protéines Escherichia coli (génétique)</term>
<term>Protéines Escherichia coli (immunologie)</term>
<term>Protéines Escherichia coli (métabolisme)</term>
<term>Protéines du choc thermique HSP70 (génétique)</term>
<term>Protéines du choc thermique HSP70 (immunologie)</term>
<term>Protéines du choc thermique HSP70 (métabolisme)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Protéines recombinantes (métabolisme)</term>
<term>Sites de fixation (génétique)</term>
<term>Structure tertiaire des protéines</term>
<term>Substitution d'acide aminé</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
<term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term>
<term>Épitopes (génétique)</term>
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<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes</term>
<term>Escherichia coli Proteins</term>
<term>HSP70 Heat-Shock Proteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Escherichia coli Proteins</term>
<term>HSP70 Heat-Shock Proteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>CD40 Ligand</term>
<term>Escherichia coli Proteins</term>
<term>HSP70 Heat-Shock Proteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Proteins</term>
<term>p38 Mitogen-Activated Protein Kinases</term>
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<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term>
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<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Dendritic Cells</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Fragments peptidiques</term>
<term>Protéines Escherichia coli</term>
<term>Protéines du choc thermique HSP70</term>
<term>Protéines recombinantes</term>
<term>Sites de fixation</term>
<term>Épitopes</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules dendritiques</term>
<term>Fragments peptidiques</term>
<term>Monocytes</term>
<term>Protéines Escherichia coli</term>
<term>Protéines du choc thermique HSP70</term>
<term>Protéines recombinantes</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term>
<term>Monocytes</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Fragments peptidiques</term>
<term>Ligand de CD40</term>
<term>Protéines Escherichia coli</term>
<term>Protéines du choc thermique HSP70</term>
<term>Protéines recombinantes</term>
<term>p38 Mitogen-Activated Protein Kinases</term>
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<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Amino Acid Substitution</term>
<term>Cell Differentiation</term>
<term>Cell Line</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Molecular Sequence Data</term>
<term>Protein Structure, Tertiary</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Différenciation cellulaire</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Structure tertiaire des protéines</term>
<term>Substitution d'acide aminé</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
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<front><div type="abstract" xml:lang="en">The 70-kDa microbial heat shock protein (mHSP70) has a profound effect on the immune system, interacting with the CD40 receptor on DC and monocytes to produce cytokines and chemokines. The mHSP70 also induces maturation of dendritic cells (DC) and thus acts as an alternative ligand to CD40L on T cells. In this investigation, we have identified a cytokine-stimulating epitope (peptide 407-426), by activating DC with overlapping synthetic peptides (20-mers) derived from the sequence of mHSP70. This peptide also significantly enhances maturation of DC stimulated by mHSP70 or CD40L. The epitope is located at the base of the peptide-binding groove of HSP70 and has five critical residues. Furthermore, an inhibitory epitope (p457-496) was identified downstream from the peptide-binding groove that inhibits cytokine production and maturation of DC stimulated by HSP70 or CD40L. The p38 MAP kinase phosphorylation is critical in the alternative CD40-HSP70 pathway and is inhibited by p457-496 but enhanced by p407-426.</div>
</front>
</TEI>
<affiliations><list><country><li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Grand Londres</li>
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<settlement><li>Londres</li>
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<tree><noCountry><name sortKey="Bergmeier, Lesley A" sort="Bergmeier, Lesley A" uniqKey="Bergmeier L" first="Lesley A" last="Bergmeier">Lesley A. Bergmeier</name>
<name sortKey="Kelly, Charles" sort="Kelly, Charles" uniqKey="Kelly C" first="Charles" last="Kelly">Charles Kelly</name>
<name sortKey="Lehner, Thomas" sort="Lehner, Thomas" uniqKey="Lehner T" first="Thomas" last="Lehner">Thomas Lehner</name>
<name sortKey="Mcgowan, Edward" sort="Mcgowan, Edward" uniqKey="Mcgowan E" first="Edward" last="Mcgowan">Edward Mcgowan</name>
<name sortKey="Singh, Mahavir" sort="Singh, Mahavir" uniqKey="Singh M" first="Mahavir" last="Singh">Mahavir Singh</name>
<name sortKey="Whittall, Trevor" sort="Whittall, Trevor" uniqKey="Whittall T" first="Trevor" last="Whittall">Trevor Whittall</name>
<name sortKey="Younson, Justine" sort="Younson, Justine" uniqKey="Younson J" first="Justine" last="Younson">Justine Younson</name>
</noCountry>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Wang, Yufei" sort="Wang, Yufei" uniqKey="Wang Y" first="Yufei" last="Wang">Yufei Wang</name>
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