Reference
Reference TypeLiterature
TitleComputer-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.
AuthorsR Al-Attiyah; A S Mustafa
AffiliationsDepartment of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait. alattiyah@hsc.kuniv.edu.kw.
JournalScand J Immunol
Year2004
AbstractThe 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 Updated2023-08-18 20:01:50
Epitope
Epitope ID33972
Chemical TypeLinear peptide
Linear SequenceKVDSLLGITSADVDVRANPLAAKGV
Source Molecule NamePutative lipoprotein lppX precursor
Source OrganismMycobacterium tuberculosis
Starting Position76
Ending Position100
Epitope Reference Details
Epitope Structure DefinesEpitope containing region/antigenic site
Epitope Namep6
Reference Starting Position76
Reference Ending Position100
Location of Data in ReferenceFigure 1
Immunization
Host OrganismHomo sapiens (human)
Host Details
MHC Types presentHLA-DR52;HLA-DR13;HLA-DR3;HLA-DR4;HLA-DR7;HLA-DR53
1st In Vivo Process
In Vivo Process TypeProphylactic vaccinationVO:0005374
Disease Statehealthy
1st Immunogen
Epitope RelationTaxonomic Sibling
Object TypeOrganism
OrganismMycobacterium tuberculosis variant bovis BCG
Immunogen Details
Immunogen Reference NameM. bovis BCG vaccine
Immunization Comments
Immunization CommentsDonors were bacille Calmette-Guérin (BCG)-vaccinated healthy subjects.
T Cell Assay
Qualitative MeasurementPositive
Method/Techniquebioassay
Measurement ofIFNg release
Measurement Details
Number of Subjects Tested17
Number of Subjects Responded3
Response Frequency (%)17.6
Effector Cells
Effector Cell Tissue TypeBlood
Effector Cell TypePBMC
Effector Cell Culture ConditionsDirect Ex Vivo
Antigen Presenting Cells
Cell Tissue TypeBlood
Cell TypePBMC
Cell Culture ConditionsDirect Ex Vivo
Antigen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceKVDSLLGITSADVDVRANPLAAKGV
Source Molecule NamePutative lipoprotein lppX precursor
Source OrganismMycobacterium tuberculosis
Starting Position76
Ending Position100
Antigen Details
Antigen Reference Namep6
Assay Reference Details
Assay Comments by IEDB CuratorThe donors were HLA-typed but the restriction was not determined.
Location of Assay Data in ReferenceTable 4