Reference
Reference TypeLiterature
IEDB_Reference:1019160
TitleMycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity.
AuthorsSimone A Joosten; Krista E van Meijgaarden; Pascale C van Weeren; Fatima Kazi; Annemieke Geluk; Nigel D L Savage; Jan W Drijfhout; Darren R Flower; Willem A Hanekom; Michèl R Klein; Tom H M Ottenhoff
AffiliationsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
JournalPLoS Pathog
PMID:20195504
Year2010
AbstractTuberculosis (TB) is an escalating global health problem and improved vaccines against TB are urgently needed. HLA-E restricted responses may be of interest for vaccine development since HLA-E displays very limited polymorphism (only 2 coding variants exist), and is not down-regulated by HIV-infection. The peptides from Mycobacterium tuberculosis (Mtb) potentially presented by HLA-E molecules, however, are unknown. Here we describe human T-cell responses to Mtb-derived peptides containing predicted HLA-E binding motifs and binding-affinity for HLA-E. We observed CD8(+) T-cell proliferation to the majority of the 69 peptides tested in Mtb responsive adults as well as in BCG-vaccinated infants. CD8(+) T-cells were cytotoxic against target-cells transfected with HLA-E only in the presence of specific peptide. These T cells were also able to lyse M. bovis BCG infected, but not control monocytes, suggesting recognition of antigens during mycobacterial infection. In addition, peptide induced CD8(+) T-cells also displayed regulatory activity, since they inhibited T-cell proliferation. This regulatory activity was cell contact-dependent, and at least partly dependent on membrane-bound TGF-beta. Our results significantly increase our understanding of the human immune response to Mtb by identification of CD8(+) T-cell responses to novel HLA-E binding peptides of Mtb, which have cytotoxic as well as immunoregulatory activity.
Curation Last Updated2024-04-29 20:02:30
Epitope
Epitope ID144956
IEDB_epitope:144956
Chemical TypeLinear peptide
Linear SequenceSMADRAENL
Source Molecule NameBifunctional enzyme CysN/CysC
GenPept:Q10600.1
Source OrganismMycobacterium tuberculosis
NCBITaxon:1773
Starting Position493
Ending Position501
Epitope Reference Details
Epitope Structure DefinesExact Epitope
Epitope NameMtb Peptide 1
Location of Data in ReferenceTable 1
Immunization
Host OrganismHomo sapiens (human)
NCBITaxon:9606
Host Details
Host GeolocationEurope
GAZ:00000464
1st In Vivo Process
In Vivo Process TypeExposure with existing immune reactivity without evidence for disease
OBI:1110061
1st Immunogen
Epitope RelationSource Organism
Object TypeOrganism
OrganismMycobacterium tuberculosis
NCBITaxon:1773
Immunization Comments
Immunization CommentsPBMC were from healthy donors who had not received BCG vaccination. Donor cells were responsive to Mtb PPD as measured by IFNγ assay.
T Cell Assay
Qualitative MeasurementPositive
Method/TechniqueCFSE
OBI:0002096
Measurement ofproliferation
Measurement Details
Number of Subjects Tested10
Number of Subjects Responded1
Response Frequency (%)10
Effector Cells
Effector Cell Tissue TypeBlood
UBERON:0000178
Effector Cell TypeT cell CD8+
CL:0000625
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-E*01:03
MRO:0001352
MHC Evidence CodeMHC binding prediction
ECO:0008081
Antigen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceSMADRAENL
Source Molecule NameBifunctional enzyme CysN/CysC
GenPept:Q10600.1
Source OrganismMycobacterium tuberculosis
NCBITaxon:1773
Starting Position493
Ending Position501
Assay Reference Details
Assay Comments by IEDB CuratorProliferation in response to the epitope was measured by CFSE staining.
Location of Assay Data in ReferenceFigure 2