Predominant recognition of species-specific determinants of the GroES homologues from Mycobacterium leprae and M. tuberculosis.
The Mycobacterium leprae and M. tuberculosis 10,000 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-2Ad (24-34) or H-2Ed (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.
Chua-Intra
B
B
Tuberculosis & Related Infections Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.
Ivanyi
J
J
Hills
A
A
Thole
J
J
Moreno
C
C
Vordermeier
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018835:Chaperonin 10 / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D018835:Chaperonin 10; D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments