Identification and HLA restriction of naturally derived Th1-cell epitopes from the secreted Mycobacterium tuberculosis antigen 85B recognized by antigen-specific human CD4(+) T-cell lines.
Identifieur interne : 003625 ( Main/Exploration ); précédent : 003624; suivant : 003626Identification and HLA restriction of naturally derived Th1-cell epitopes from the secreted Mycobacterium tuberculosis antigen 85B recognized by antigen-specific human CD4(+) T-cell lines.
Auteurs : A S Mustafa [Koweït] ; F A Shaban ; A T Abal ; R. Al-Attiyah ; H G Wiker ; K E Lundin ; F. Oftung ; K. HuygenSource :
- Infection and immunity [ 0019-9567 ] ; 2000.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Acyltransferases, Antigènes HLA, Antigènes bactériens (génétique), Données de séquences moléculaires, Humains, Lignée cellulaire, Lymphocytes T CD4+ (immunologie), Lymphocytes auxiliaires Th1 (immunologie), Mycobacterium tuberculosis (génétique), Mycobacterium tuberculosis (immunologie), Protéines bactériennes (génétique), Protéines bactériennes (immunologie), Présentation d'antigène, Similitude de séquences d'acides aminés, Séquence d'acides aminés, Tuberculose pulmonaire (immunologie), Vaccin BCG (immunologie), Épitopes (génétique).
- MESH :
- génétique : Antigènes bactériens, Mycobacterium tuberculosis, Protéines bactériennes, Épitopes.
- immunologie : Lymphocytes T CD4+, Lymphocytes auxiliaires Th1, Mycobacterium tuberculosis, Protéines bactériennes, Tuberculose pulmonaire, Vaccin BCG.
- Activation des lymphocytes, Acyltransferases, Antigènes HLA, Données de séquences moléculaires, Humains, Lignée cellulaire, Présentation d'antigène, Similitude de séquences d'acides aminés, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Acyltransferases, Amino Acid Sequence, Antigen Presentation, Antigens, Bacterial (genetics), BCG Vaccine (immunology), Bacterial Proteins (genetics), Bacterial Proteins (immunology), CD4-Positive T-Lymphocytes (immunology), Cell Line, Epitopes (genetics), HLA Antigens, Humans, Lymphocyte Activation, Molecular Sequence Data, Mycobacterium tuberculosis (genetics), Mycobacterium tuberculosis (immunology), Sequence Homology, Amino Acid, Th1 Cells (immunology), Tuberculosis, Pulmonary (immunology).
- MESH :
- chemical , genetics : Antigens, Bacterial, Bacterial Proteins, Epitopes.
- chemical , immunology : BCG Vaccine, Bacterial Proteins.
- chemical : Acyltransferases, HLA Antigens.
- genetics : Mycobacterium tuberculosis.
- immunology : CD4-Positive T-Lymphocytes, Mycobacterium tuberculosis, Th1 Cells, Tuberculosis, Pulmonary.
- Amino Acid Sequence, Antigen Presentation, Cell Line, Humans, Lymphocyte Activation, Molecular Sequence Data, Sequence Homology, Amino Acid.
Abstract
Antigen 85B (Ag85B/MPT59) is a major secreted protein from Mycobacterium tuberculosis which is a promising candidate antigen for inclusion in novel subunit vaccines against tuberculosis (TB). The present study was undertaken to map naturally derived T-cell epitopes from M. tuberculosis Ag85B in relation to major histocompatibility complex (MHC) class II restriction. Antigen-specific CD4(+) T-cell lines were established from HLA-typed TB patients and Mycobacterium bovis BCG vaccinees by stimulation of peripheral blood mononuclear cells with purified Ag85B in vitro. The established T-cell lines were then tested for proliferation and gamma interferon (IFN-gamma) secretion in response to 31 overlapping synthetic peptides (18-mers) covering the entire sequence of the mature protein. The results showed that the epitopes recognized by T-cell lines from TB patients were scattered throughout the Ag85B sequence whereas the epitopes recognized by T-cell lines from BCG vaccinees were located toward the N-terminal part of the antigen. The T-cell epitopes represented by peptides p2 (amino acids [aa] 10 to 27), p3 (aa 19 to 36), and p11 (aa 91 to 108) were frequently recognized by antigen-specific T-cell lines from BCG vaccinees in both proliferation and IFN-gamma assays. MHC restriction analysis demonstrated that individual T-cell lines specifically recognized the complete Ag85B either in association with one of the self HLA-DRB1, DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner. At the epitope level, panel studies showed that peptides p2, p3, and p11 were presented to T cells by HLA-DR-matched as well as mismatched allogeneic antigen-presenting cells, thus representing promiscuous epitopes. The identification of naturally derived peptide epitopes from the M. tuberculosis Ag85B presented to Th1 cells in the context of multiple HLA-DR molecules strongly supports the relevance of this antigen to subunit vaccine design.
DOI: 10.1128/iai.68.7.3933-3940.2000
PubMed: 10858206
Affiliations:
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Le document en format XML
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Al-Attiyah</name></author><author><name sortKey="Wiker, H G" sort="Wiker, H G" uniqKey="Wiker H" first="H G" last="Wiker">H G Wiker</name></author><author><name sortKey="Lundin, K E" sort="Lundin, K E" uniqKey="Lundin K" first="K E" last="Lundin">K E Lundin</name></author><author><name sortKey="Oftung, F" sort="Oftung, F" uniqKey="Oftung F" first="F" last="Oftung">F. Oftung</name></author><author><name sortKey="Huygen, K" sort="Huygen, K" uniqKey="Huygen K" first="K" last="Huygen">K. Huygen</name></author></analytic><series><title level="j">Infection and immunity</title><idno type="ISSN">0019-9567</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acyltransferases</term><term>Amino Acid Sequence</term><term>Antigen Presentation</term><term>Antigens, Bacterial (genetics)</term><term>BCG Vaccine (immunology)</term><term>Bacterial Proteins (genetics)</term><term>Bacterial Proteins (immunology)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>Cell Line</term><term>Epitopes (genetics)</term><term>HLA Antigens</term><term>Humans</term><term>Lymphocyte Activation</term><term>Molecular Sequence Data</term><term>Mycobacterium tuberculosis (genetics)</term><term>Mycobacterium tuberculosis (immunology)</term><term>Sequence Homology, Amino Acid</term><term>Th1 Cells (immunology)</term><term>Tuberculosis, Pulmonary (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes</term><term>Acyltransferases</term><term>Antigènes HLA</term><term>Antigènes bactériens (génétique)</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Lignée cellulaire</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes auxiliaires Th1 (immunologie)</term><term>Mycobacterium tuberculosis (génétique)</term><term>Mycobacterium tuberculosis (immunologie)</term><term>Protéines bactériennes (génétique)</term><term>Protéines bactériennes (immunologie)</term><term>Présentation d'antigène</term><term>Similitude de séquences d'acides aminés</term><term>Séquence d'acides aminés</term><term>Tuberculose pulmonaire (immunologie)</term><term>Vaccin BCG (immunologie)</term><term>Épitopes (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Bacterial</term><term>Bacterial Proteins</term><term>Epitopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>BCG Vaccine</term><term>Bacterial Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Acyltransferases</term><term>HLA Antigens</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mycobacterium tuberculosis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes bactériens</term><term>Mycobacterium tuberculosis</term><term>Protéines bactériennes</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T CD4+</term><term>Lymphocytes auxiliaires Th1</term><term>Mycobacterium tuberculosis</term><term>Protéines bactériennes</term><term>Tuberculose pulmonaire</term><term>Vaccin BCG</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Mycobacterium tuberculosis</term><term>Th1 Cells</term><term>Tuberculosis, Pulmonary</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigen Presentation</term><term>Cell Line</term><term>Humans</term><term>Lymphocyte Activation</term><term>Molecular Sequence Data</term><term>Sequence Homology, Amino Acid</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term><term>Acyltransferases</term><term>Antigènes HLA</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Lignée cellulaire</term><term>Présentation d'antigène</term><term>Similitude de séquences d'acides aminés</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Antigen 85B (Ag85B/MPT59) is a major secreted protein from Mycobacterium tuberculosis which is a promising candidate antigen for inclusion in novel subunit vaccines against tuberculosis (TB). The present study was undertaken to map naturally derived T-cell epitopes from M. tuberculosis Ag85B in relation to major histocompatibility complex (MHC) class II restriction. Antigen-specific CD4(+) T-cell lines were established from HLA-typed TB patients and Mycobacterium bovis BCG vaccinees by stimulation of peripheral blood mononuclear cells with purified Ag85B in vitro. The established T-cell lines were then tested for proliferation and gamma interferon (IFN-gamma) secretion in response to 31 overlapping synthetic peptides (18-mers) covering the entire sequence of the mature protein. The results showed that the epitopes recognized by T-cell lines from TB patients were scattered throughout the Ag85B sequence whereas the epitopes recognized by T-cell lines from BCG vaccinees were located toward the N-terminal part of the antigen. The T-cell epitopes represented by peptides p2 (amino acids [aa] 10 to 27), p3 (aa 19 to 36), and p11 (aa 91 to 108) were frequently recognized by antigen-specific T-cell lines from BCG vaccinees in both proliferation and IFN-gamma assays. MHC restriction analysis demonstrated that individual T-cell lines specifically recognized the complete Ag85B either in association with one of the self HLA-DRB1, DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner. At the epitope level, panel studies showed that peptides p2, p3, and p11 were presented to T cells by HLA-DR-matched as well as mismatched allogeneic antigen-presenting cells, thus representing promiscuous epitopes. The identification of naturally derived peptide epitopes from the M. tuberculosis Ag85B presented to Th1 cells in the context of multiple HLA-DR molecules strongly supports the relevance of this antigen to subunit vaccine design.</div></front></TEI><affiliations><list><country><li>Koweït</li></country></list><tree><noCountry><name sortKey="Abal, A T" sort="Abal, A T" uniqKey="Abal A" first="A T" last="Abal">A T Abal</name><name sortKey="Al Attiyah, R" sort="Al Attiyah, R" uniqKey="Al Attiyah R" first="R" last="Al-Attiyah">R. Al-Attiyah</name><name sortKey="Huygen, K" sort="Huygen, K" uniqKey="Huygen K" first="K" last="Huygen">K. Huygen</name><name sortKey="Lundin, K E" sort="Lundin, K E" uniqKey="Lundin K" first="K E" last="Lundin">K E Lundin</name><name sortKey="Oftung, F" sort="Oftung, F" uniqKey="Oftung F" first="F" last="Oftung">F. Oftung</name><name sortKey="Shaban, F A" sort="Shaban, F A" uniqKey="Shaban F" first="F A" last="Shaban">F A Shaban</name><name sortKey="Wiker, H G" sort="Wiker, H G" uniqKey="Wiker H" first="H G" last="Wiker">H G Wiker</name></noCountry><country name="Koweït"><noRegion><name sortKey="Mustafa, A S" sort="Mustafa, A S" uniqKey="Mustafa A" first="A S" last="Mustafa">A S Mustafa</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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