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Predominant recognition of species-specific determinants of the GroES homologues from Mycobacterium leprae and M. tuberculosis

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Author: Chua-Intra, B. · Ivanyi, J. · Hills, A. · Thole, J. · Moreno, C. · Vordermeier, H.M.
Type:article
Date:1998
Institution: TNO Preventie en Gezondheid
Source:Immunology, 1, 93, 64-72
Identifier: 234429
doi: DOI:10.1046/j.1365-2567.1998.00400.x
Keywords: Health · Animal experiment · Animal model · Antibody specificity · Antigen recognition · Bacterial membrane · Controlled study · Delayed hypersensitivity · Hybridoma · Mouse · Mycobacterium leprae · Mycobacterium tuberculosis · Nonhuman · Pleura fluid · Species difference · Stem cell · Amino Acid Sequence · Animals · Antigens, Bacterial · B-Lymphocytes · Chaperonin 10 · Epitope Mapping · Epitopes · Female · H-2 Antigens · Mice · Mice, Inbred Strains · Mycobacterium leprae · Mycobacterium tuberculosis · Peptide Fragments · Species Specificity · T-Lymphocytes

Abstract

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