Reference
Reference TypeLiterature
IEDB_Reference:1012363
TitleEfficient testing of large pools of Mycobacterium tuberculosis RD1 peptides and identification of major antigens and immunodominant peptides recognized by human Th1 cells.
AuthorsAbu S Mustafa; Raja'a Al-Attiyah; Sumaila N M Hanif; Fatema A Shaban
AffiliationsDepartment of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. abusalim@hsc.edu.kw.
JournalClin Vaccine Immunol
PMID:18400977
Year2008
AbstractComparative genomics has identified several regions of difference (RDs) of Mycobacterium tuberculosis that are deleted or absent in Mycobacterium bovis BCG vaccines. To determine their relevance for diagnostic and vaccine applications, it is imperative that efficient methods are developed to test the encoded proteins for immunological reactivity. In this study, we have used 220 synthetic peptides covering sequences of 12 open reading frames (ORFs) of RD1 and tested them as a single pool (RD1(pool)) with peripheral blood mononuclear cells obtained from pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects in Th1 cell assays that measure antigen-induced proliferation and IFN-gamma secretion. The results showed that RD1(pool) induced strong responses in both TB patients and BCG-vaccinated healthy subjects. The subsequent testing of peptide pools of individual ORFs revealed that all ORFs induced positive responses in a portion of donors, but PPE68, CFP10, and ESAT6 induced strong responses in TB patients and PPE68 induced strong responses in BCG-vaccinated healthy subjects. In addition, HLA-DR and -DQ typing of donors and HLA-DR binding prediction analysis of proteins suggested HLA-promiscuous presentation of PPE68, CFP10, and ESAT6. Further testing of individual peptides showed that a single peptide of PPE68 (121-VLTATNFFGINTIPIALTEMDYFIR-145) was immunodominant. The search for sequence homology revealed that a part of this peptide, 124-ATNFFGINTIPIAL-137, was present in several PPE family proteins of M. tuberculosis and M. bovis BCG vaccines. Further experiments limited the promiscuous and immunodominant epitope region to the 10-amino-acid cross-reactive sequence 127-FFGINTIPIA-136.
Curation Last Updated2023-08-18 20:34:54
Epitope
Epitope ID15812
IEDB_epitope:15812
Chemical TypeLinear peptide
Linear SequenceFFGINTIPIA
Source Molecule NamePPE FAMILY PROTEIN
GenPept:YP_178022.1
Source OrganismMycobacterium tuberculosis
NCBITaxon:1773
Starting Position124
Ending Position133
Epitope Reference Details
Epitope Structure DefinesExact Epitope
Epitope NamePPE68 127-136
Reference Starting Position127
Reference Ending Position136
Location of Data in ReferenceTable 5
Immunization
Host OrganismHomo sapiens (human)
NCBITaxon:9606
1st In Vivo Process
In Vivo Process TypeProphylactic vaccinationVO:0005374
Disease Statehealthy
ONTIE:0003423
1st Immunogen
Epitope RelationTaxonomic Sibling
Object TypeOrganism
OrganismMycobacterium tuberculosis variant bovis BCG
NCBITaxon:33892
Immunogen Details
Immunogen Reference NameBCG vaccine
T Cell Assay
Qualitative MeasurementPositive
Method/TechniqueELISA
OBI:1110151
Measurement ofIFNg release
Measurement Details
Number of Subjects Tested8
Number of Subjects Responded8
Response Frequency (%)100
Effector Cells
Effector Cell Tissue TypeBlood
UBERON:0000178
Effector Cell TypePBMC
CL:2000001
Effector Cell Culture ConditionsDirect Ex Vivo
Antigen Presenting Cells
Cell Tissue TypeBlood
UBERON:0000178
Cell TypePBMC
CL:2000001
Cell Culture ConditionsDirect Ex Vivo
MHC Allele
MHC Allele NameHLA-DR
MRO:0000013
MHC Evidence CodeMHC binding prediction
ECO:0008081
Antigen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceFFGINTIPIA
Source Molecule NamePPE FAMILY PROTEIN
GenPept:YP_178022.1
Source OrganismMycobacterium tuberculosis
NCBITaxon:1773
Starting Position124
Ending Position133
Assay Reference Details
Location of Assay Data in ReferenceTable 5