Predominant recognition of species-specific determinants of the GroES homologues from Mycobacterium leprae and M. tuberculosis
article
The Mycobacterium leprae and M. tuberculosis 10000 MW heat-shock protein homologues of GroES have previously been identified as major immunogens for human T cells. We used synthetic peptides to characterize the determinants recognized by murine T cells. The findings suggest that, despite 90% sequence identity between these two proteins, T cells recognize prominently the species-specific determinants localized within amino acid residues 21-40 and 49-72. Analysis of the molecular determinants of species-specificity for the M. leprae GroES sequence 25-40, using T-cell hybridomas and major histocompatibility complex (MHC)-binding assays, led to the identification of epitope cores and critical residues. Interestingly, closely overlapping epitope cores were found to be restricted by either H-2A(d) (24-34) or H- 2E(d) (28-34). Furthermore, the site recognized by the M. leprae-specific monoclonal antibodies ML06 and ML10 was also localized in the overlapping sequences 25-31 and 25-29. In conclusion, we demonstrated that immunodominant species-specific T- and B-cell epitopes can be found in a mycobacterial heat- shock protein despite its highly conserved amino acid sequence. This finding suggests the feasibility of identifying a sufficient number of M. leprae- specific determinants for a composite T-cell immunodiagnostic reagent for tuberculoid leprosy. Chemicals/CAS: Antigens, Bacterial; Chaperonin 10; Epitopes; H-2 Antigens; Peptide Fragments
Topics
Animal experimentAnimal modelAntibody specificityAntigen recognitionBacterial membraneControlled studyDelayed hypersensitivityHybridomaMouseMycobacterium lepraeMycobacterium tuberculosisNonhumanPleura fluidSpecies differenceStem cellAmino Acid SequenceAnimalsAntigens, BacterialB-LymphocytesChaperonin 10Epitope MappingEpitopesFemaleH-2 AntigensMiceMice, Inbred StrainsMycobacterium lepraeMycobacterium tuberculosisPeptide FragmentsSpecies SpecificityT-Lymphocytes
TNO Identifier
234429
ISSN
00192805
Source
Immunology, 93(1), pp. 64-72.
Pages
64-72
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