Synthetic peptides identify promiscuous human Th1 cell epitopes of the secreted mycobacterial antigen MPB70.
Identifieur interne : 003225 ( Main/Merge ); précédent : 003224; suivant : 003226Synthetic peptides identify promiscuous human Th1 cell epitopes of the secreted mycobacterial antigen MPB70.
Auteurs : Raja Al-Attiyah [Koweït] ; Fatema A. Shaban ; Harald G. Wiker ; Fredrik Oftung ; Abu S. MustafaSource :
- Infection and immunity [ 0019-9567 ] ; 2003.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Antigènes HLA-DR (métabolisme), Antigènes bactériens (immunologie), Cartographie épitopique, Cytotoxicité immunologique, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T, Humains, Interféron gamma, Lignée cellulaire, Lymphocytes T CD4+ (immunologie), Lymphocytes auxiliaires Th1 (immunologie), Mycobacterium tuberculosis (immunologie), Peptides (), Peptides (immunologie), Peptides (synthèse chimique), Protéines bactériennes (), Protéines bactériennes (immunologie), Séquence d'acides aminés, Tuberculose (), Tuberculose (immunologie), Vaccin BCG (immunologie), Épitopes immunodominants.
- MESH :
- immunologie : Antigènes bactériens, Lymphocytes T CD4+, Lymphocytes auxiliaires Th1, Mycobacterium tuberculosis, Peptides, Protéines bactériennes, Tuberculose, Vaccin BCG.
- métabolisme : Antigènes HLA-DR.
- synthèse chimique : Peptides.
- Activation des lymphocytes, Cartographie épitopique, Cytotoxicité immunologique, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T, Humains, Interféron gamma, Lignée cellulaire, Peptides, Protéines bactériennes, Séquence d'acides aminés, Tuberculose, Épitopes immunodominants.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antigens, Bacterial (immunology), BCG Vaccine (immunology), Bacterial Proteins (chemistry), Bacterial Proteins (immunology), CD4-Positive T-Lymphocytes (immunology), Cell Line, Cytotoxicity, Immunologic, Epitope Mapping, Epitopes, T-Lymphocyte, HLA-DR Antigens (metabolism), Humans, Immunodominant Epitopes, Interferon-gamma, Lymphocyte Activation, Molecular Sequence Data, Mycobacterium tuberculosis (immunology), Peptides (chemical synthesis), Peptides (chemistry), Peptides (immunology), Th1 Cells (immunology), Tuberculosis (immunology), Tuberculosis (prevention & control).
- MESH :
- chemical , chemical synthesis : Peptides.
- chemical , chemistry : Bacterial Proteins, Peptides.
- chemical , immunology : Antigens, Bacterial, BCG Vaccine, Bacterial Proteins, Peptides.
- immunology : CD4-Positive T-Lymphocytes, Mycobacterium tuberculosis, Th1 Cells, Tuberculosis.
- chemical , metabolism : HLA-DR Antigens.
- prevention & control : Tuberculosis.
- Amino Acid Sequence, Cell Line, Cytotoxicity, Immunologic, Epitope Mapping, Epitopes, T-Lymphocyte, Humans, Immunodominant Epitopes, Interferon-gamma, Lymphocyte Activation, Molecular Sequence Data.
Abstract
MPB70 is a secreted protein of Mycobacterium bovis and Mycobacterium tuberculosis which stimulates both cellular and humoral immune responses during infection with bovine and human tubercle bacilli. In addition, vaccination with MPB70 has been shown to induce Th1 cell responses and protection in animal models of tuberculosis. The present study was carried out to map the dominant human Th1 cell epitopes of MPB70 in relation to major histocompatibility complex (MHC) class II restriction in healthy subjects showing strong T-cell responses to complex mycobacterial antigens. Peripheral blood mononuclear cells (PBMC) from HLA-DR-typed donors were tested with complex mycobacterial antigens (whole-cell M. tuberculosis and M. tuberculosis culture filtrates), with MPB70 purified from the culture filtrate of M. bovis BCG Tokyo, and with 13 synthetic peptides (25-mers overlapping by 10 residues) covering the sequence of MPB70. The donors that responded to the complex antigens and MPB70 also responded to the cocktail of synthetic MPB70 peptides. Testing of PBMC with individual peptides showed that peptides p5 (amino acids [aa] 61 to 85), p6 (aa 76 to 100), p8 (aa 106 to 130), p12 (aa 166 to 190), and p13 (aa 181 to 193) were most frequently recognized in proliferation and gamma interferon (IFN-gamma) assays. Testing of antigen-specific CD4(+) T-cell lines with the individual peptides of MPB70 confirmed that peptides p8, p12, and p13 contain immunodominant Th1 cell epitopes of MPB70. MHC restriction analysis with HLA-typed donors showed that MPB70 and its immunodominant peptides were presented to T cells promiscuously. The T-cell lines responding to MPB70 and peptides p8, p12, and p13 in IFN-gamma assays mediated antigen-peptide-specific cytotoxic activity against monocytes/macrophages pulsed with the whole-protein antigen or the peptides. In conclusion, the promiscuous recognition of MPB70 and its immunodominant peptide defined epitopes (aa 106 to 130 and 166 to 193) by IFN-gamma-producing Th1 cells supports possible application of this secreted antigen to subunit vaccine design.
DOI: 10.1128/iai.71.4.1953-1960.2003
PubMed: 12654813
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pubmed:12654813Le document en format XML
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<term>Antigens, Bacterial (immunology)</term>
<term>BCG Vaccine (immunology)</term>
<term>Bacterial Proteins (chemistry)</term>
<term>Bacterial Proteins (immunology)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>Cell Line</term>
<term>Cytotoxicity, Immunologic</term>
<term>Epitope Mapping</term>
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-DR Antigens (metabolism)</term>
<term>Humans</term>
<term>Immunodominant Epitopes</term>
<term>Interferon-gamma</term>
<term>Lymphocyte Activation</term>
<term>Molecular Sequence Data</term>
<term>Mycobacterium tuberculosis (immunology)</term>
<term>Peptides (chemical synthesis)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (immunology)</term>
<term>Th1 Cells (immunology)</term>
<term>Tuberculosis (immunology)</term>
<term>Tuberculosis (prevention & control)</term>
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<term>Cartographie épitopique</term>
<term>Cytotoxicité immunologique</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
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<term>Lignée cellulaire</term>
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<term>Séquence d'acides aminés</term>
<term>Tuberculose ()</term>
<term>Tuberculose (immunologie)</term>
<term>Vaccin BCG (immunologie)</term>
<term>Épitopes immunodominants</term>
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<term>Peptides</term>
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<term>Tuberculose</term>
<term>Vaccin BCG</term>
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<term>Mycobacterium tuberculosis</term>
<term>Th1 Cells</term>
<term>Tuberculosis</term>
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<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Peptides</term>
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<term>Cell Line</term>
<term>Cytotoxicity, Immunologic</term>
<term>Epitope Mapping</term>
<term>Epitopes, T-Lymphocyte</term>
<term>Humans</term>
<term>Immunodominant Epitopes</term>
<term>Interferon-gamma</term>
<term>Lymphocyte Activation</term>
<term>Molecular Sequence Data</term>
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<term>Cartographie épitopique</term>
<term>Cytotoxicité immunologique</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Humains</term>
<term>Interféron gamma</term>
<term>Lignée cellulaire</term>
<term>Peptides</term>
<term>Protéines bactériennes</term>
<term>Séquence d'acides aminés</term>
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<front><div type="abstract" xml:lang="en">MPB70 is a secreted protein of Mycobacterium bovis and Mycobacterium tuberculosis which stimulates both cellular and humoral immune responses during infection with bovine and human tubercle bacilli. In addition, vaccination with MPB70 has been shown to induce Th1 cell responses and protection in animal models of tuberculosis. The present study was carried out to map the dominant human Th1 cell epitopes of MPB70 in relation to major histocompatibility complex (MHC) class II restriction in healthy subjects showing strong T-cell responses to complex mycobacterial antigens. Peripheral blood mononuclear cells (PBMC) from HLA-DR-typed donors were tested with complex mycobacterial antigens (whole-cell M. tuberculosis and M. tuberculosis culture filtrates), with MPB70 purified from the culture filtrate of M. bovis BCG Tokyo, and with 13 synthetic peptides (25-mers overlapping by 10 residues) covering the sequence of MPB70. The donors that responded to the complex antigens and MPB70 also responded to the cocktail of synthetic MPB70 peptides. Testing of PBMC with individual peptides showed that peptides p5 (amino acids [aa] 61 to 85), p6 (aa 76 to 100), p8 (aa 106 to 130), p12 (aa 166 to 190), and p13 (aa 181 to 193) were most frequently recognized in proliferation and gamma interferon (IFN-gamma) assays. Testing of antigen-specific CD4(+) T-cell lines with the individual peptides of MPB70 confirmed that peptides p8, p12, and p13 contain immunodominant Th1 cell epitopes of MPB70. MHC restriction analysis with HLA-typed donors showed that MPB70 and its immunodominant peptides were presented to T cells promiscuously. The T-cell lines responding to MPB70 and peptides p8, p12, and p13 in IFN-gamma assays mediated antigen-peptide-specific cytotoxic activity against monocytes/macrophages pulsed with the whole-protein antigen or the peptides. In conclusion, the promiscuous recognition of MPB70 and its immunodominant peptide defined epitopes (aa 106 to 130 and 166 to 193) by IFN-gamma-producing Th1 cells supports possible application of this secreted antigen to subunit vaccine design.</div>
</front>
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