Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis.
Identifieur interne : 003073 ( Main/Exploration ); précédent : 003072; suivant : 003074Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis.
Auteurs : R. Al-Attiyah [Koweït] ; A S MustafaSource :
- Scandinavian journal of immunology [ 0300-9475 ] ; 2004.
Descripteurs français
- KwdFr :
- Animaux, Antigènes HLA-DR (immunologie), Antigènes HLA-DR (métabolisme), Antigènes bactériens (immunologie), Cartographie épitopique (), Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T (), Humains, Lymphocytes auxiliaires Th1 (immunologie), Lymphocytes auxiliaires Th1 (métabolisme), Mycobacterium tuberculosis (immunologie), Peptides (immunologie), Peptides (métabolisme), Similitude de séquences, Simulation numérique, Séquence d'acides aminés, Vaccin BCG.
- MESH :
- immunologie : Antigènes HLA-DR, Antigènes bactériens, Lymphocytes auxiliaires Th1, Mycobacterium tuberculosis, Peptides.
- métabolisme : Antigènes HLA-DR, Lymphocytes auxiliaires Th1, Peptides.
- Animaux, Cartographie épitopique, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T, Humains, Similitude de séquences, Simulation numérique, Séquence d'acides aminés, Vaccin BCG.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antigens, Bacterial (immunology), BCG Vaccine, Computer Simulation, Epitope Mapping (methods), Epitopes, T-Lymphocyte (chemistry), HLA-DR Antigens (immunology), HLA-DR Antigens (metabolism), Humans, Molecular Sequence Data, Mycobacterium tuberculosis (immunology), Peptides (immunology), Peptides (metabolism), Sequence Homology, Th1 Cells (immunology), Th1 Cells (metabolism).
- MESH :
- chemical , chemistry : Epitopes, T-Lymphocyte.
- chemical , immunology : Antigens, Bacterial, HLA-DR Antigens, Peptides.
- chemical , metabolism : HLA-DR Antigens, Peptides.
- immunology : Mycobacterium tuberculosis, Th1 Cells.
- metabolism : Th1 Cells.
- methods : Epitope Mapping.
- Amino Acid Sequence, Animals, BCG Vaccine, Computer Simulation, Humans, Molecular Sequence Data, Sequence Homology.
Abstract
The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for Mycobacterium tuberculosis complex and M. leprae. The present study was carried out to identify the promiscuous T helper 1 (Th1)-cell epitopes of the M. tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic peptides (25 mers overlapping by 10 residues) covering the sequence of the complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of nine serologically defined HLA-DR molecules, by using a virtual matrix-based prediction program (propred), showed that eight of the 15 peptides of Rv2945c were predicted to bind promiscuously to >/=10 alleles from more than or equal to three serologically defined HLA-DR molecules. The Th1-cell reactivity of all the peptides was assessed in antigen-induced proliferation and interferon-gamma (IFN-gamma)-secretion assays with peripheral blood mononuclear cells (PBMCs) from 37 bacille Calmette-Guérin (BCG)-vaccinated healthy subjects. The results showed that 17 of the 37 donors, which represented an HLA-DR-heterogeneous group, responded to one or more peptides of Rv2945c in the Th1-cell assays. Although each peptide stimulated PBMCs from one or more donors in the above assays, the best positive responses (12/17 (71%) responders) were observed with the peptide p14 (aa 196-220). This suggested a highly promiscuous presentation of p14 to Th1 cells. In addition, the sequence of p14 is completely identical among the LppX of M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of Rv2945c and p14 in the subunit vaccine design against both tuberculosis and leprosy.
DOI: 10.1111/j.0300-9475.2004.01349.x
PubMed: 14723617
Affiliations:
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Al-Attiyah</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait. alattiyah@hsc.kuniv.edu.kw</nlm:affiliation><country xml:lang="fr">Koweït</country><wicri:regionArea>Department of Microbiology, Faculty of Medicine, Kuwait University, Safat</wicri:regionArea><wicri:noRegion>Safat</wicri:noRegion></affiliation></author><author><name sortKey="Mustafa, A S" sort="Mustafa, A S" uniqKey="Mustafa A" first="A S" last="Mustafa">A S Mustafa</name></author></analytic><series><title level="j">Scandinavian journal of immunology</title><idno type="ISSN">0300-9475</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antigens, Bacterial (immunology)</term><term>BCG Vaccine</term><term>Computer Simulation</term><term>Epitope Mapping (methods)</term><term>Epitopes, T-Lymphocyte (chemistry)</term><term>HLA-DR Antigens (immunology)</term><term>HLA-DR Antigens (metabolism)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Mycobacterium tuberculosis (immunology)</term><term>Peptides (immunology)</term><term>Peptides (metabolism)</term><term>Sequence Homology</term><term>Th1 Cells (immunology)</term><term>Th1 Cells (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigènes HLA-DR (immunologie)</term><term>Antigènes HLA-DR (métabolisme)</term><term>Antigènes bactériens (immunologie)</term><term>Cartographie épitopique ()</term><term>Données de séquences moléculaires</term><term>Déterminants antigéniques des lymphocytes T ()</term><term>Humains</term><term>Lymphocytes auxiliaires Th1 (immunologie)</term><term>Lymphocytes auxiliaires Th1 (métabolisme)</term><term>Mycobacterium tuberculosis (immunologie)</term><term>Peptides (immunologie)</term><term>Peptides (métabolisme)</term><term>Similitude de séquences</term><term>Simulation numérique</term><term>Séquence d'acides aminés</term><term>Vaccin BCG</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes, T-Lymphocyte</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Bacterial</term><term>HLA-DR Antigens</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HLA-DR Antigens</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes HLA-DR</term><term>Antigènes bactériens</term><term>Lymphocytes auxiliaires Th1</term><term>Mycobacterium tuberculosis</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Mycobacterium tuberculosis</term><term>Th1 Cells</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Th1 Cells</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Epitope Mapping</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes HLA-DR</term><term>Lymphocytes auxiliaires Th1</term><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>BCG Vaccine</term><term>Computer Simulation</term><term>Humans</term><term>Molecular Sequence Data</term><term>Sequence Homology</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie épitopique</term><term>Données de séquences moléculaires</term><term>Déterminants antigéniques des lymphocytes T</term><term>Humains</term><term>Similitude de séquences</term><term>Simulation numérique</term><term>Séquence d'acides aminés</term><term>Vaccin BCG</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for Mycobacterium tuberculosis complex and M. leprae. The present study was carried out to identify the promiscuous T helper 1 (Th1)-cell epitopes of the M. tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic peptides (25 mers overlapping by 10 residues) covering the sequence of the complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of nine serologically defined HLA-DR molecules, by using a virtual matrix-based prediction program (propred), showed that eight of the 15 peptides of Rv2945c were predicted to bind promiscuously to >/=10 alleles from more than or equal to three serologically defined HLA-DR molecules. The Th1-cell reactivity of all the peptides was assessed in antigen-induced proliferation and interferon-gamma (IFN-gamma)-secretion assays with peripheral blood mononuclear cells (PBMCs) from 37 bacille Calmette-Guérin (BCG)-vaccinated healthy subjects. The results showed that 17 of the 37 donors, which represented an HLA-DR-heterogeneous group, responded to one or more peptides of Rv2945c in the Th1-cell assays. Although each peptide stimulated PBMCs from one or more donors in the above assays, the best positive responses (12/17 (71%) responders) were observed with the peptide p14 (aa 196-220). This suggested a highly promiscuous presentation of p14 to Th1 cells. In addition, the sequence of p14 is completely identical among the LppX of M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of Rv2945c and p14 in the subunit vaccine design against both tuberculosis and leprosy.</div></front></TEI><affiliations><list><country><li>Koweït</li></country></list><tree><noCountry><name sortKey="Mustafa, A S" sort="Mustafa, A S" uniqKey="Mustafa A" first="A S" last="Mustafa">A S Mustafa</name></noCountry><country name="Koweït"><noRegion><name sortKey="Al Attiyah, R" sort="Al Attiyah, R" uniqKey="Al Attiyah R" first="R" last="Al-Attiyah">R. Al-Attiyah</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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