Reference | ||
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Reference Type | Literature | IEDB_Reference:656 |
Title | 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. | |
Authors | R Al-Attiyah; A S Mustafa | |
Affiliations | Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait. alattiyah@hsc.kuniv.edu.kw. | |
Journal | Scand J Immunol | |
Year | 2004 | |
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. | |
Curation Last Updated | 2023-08-18 20:01:50 |
Epitope | ||
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Epitope ID | 33972 | IEDB_epitope:33972 |
Chemical Type | Linear peptide | |
Linear Sequence | KVDSLLGITSADVDVRANPLAAKGV | |
Source Molecule Name | Putative lipoprotein lppX precursor | |
Source Organism | Mycobacterium tuberculosis | |
Starting Position | 76 | |
Ending Position | 100 |
Epitope Reference Details | ||
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Epitope Structure Defines | Epitope containing region/antigenic site | |
Epitope Name | p6 | |
Reference Starting Position | 76 | |
Reference Ending Position | 100 | |
Location of Data in Reference | Figure 1 |
Immunization | ||
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Host Organism | Homo sapiens (human) |
Host Details | ||
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MHC Types present | HLA-DR52;HLA-DR13;HLA-DR3;HLA-DR4;HLA-DR7;HLA-DR53 |
1st In Vivo Process | ||
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In Vivo Process Type | Prophylactic vaccination | VO:0005374 |
Disease State | healthy |
1st Immunogen | ||
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Epitope Relation | Taxonomic Sibling | |
Object Type | Organism | |
Organism | Mycobacterium tuberculosis variant bovis BCG |
Immunogen Details | ||
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Immunogen Reference Name | M. bovis BCG vaccine |
Immunization Comments | ||
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Immunization Comments | Donors were bacille Calmette-Guérin (BCG)-vaccinated healthy subjects. |
T Cell Assay | ||
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Qualitative Measurement | Positive | |
Method/Technique | bioassay | |
Measurement of | IFNg release |
Measurement Details | ||
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Number of Subjects Tested | 17 | |
Number of Subjects Responded | 3 | |
Response Frequency (%) | 17.6 |
Effector Cells | ||
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Effector Cell Tissue Type | Blood | |
Effector Cell Type | PBMC | |
Effector Cell Culture Conditions | Direct Ex Vivo |
Antigen Presenting Cells | ||
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Cell Tissue Type | Blood | |
Cell Type | PBMC | |
Cell Culture Conditions | Direct Ex Vivo |
Antigen | ||
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Epitope Relation | Epitope | |
Chemical Type | Linear peptide | |
Linear Sequence | KVDSLLGITSADVDVRANPLAAKGV | |
Source Molecule Name | Putative lipoprotein lppX precursor | |
Source Organism | Mycobacterium tuberculosis | |
Starting Position | 76 | |
Ending Position | 100 |
Antigen Details | ||
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Antigen Reference Name | p6 |
Assay Reference Details | ||
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Assay Comments by IEDB Curator | The donors were HLA-typed but the restriction was not determined. | |
Location of Assay Data in Reference | Table 4 |