Comparative Analysis of B- and T-Cell Epitopes ofMycobacterium lepraeandMycobacterium tuberculosisCulture Filtrate Protein 10

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Abstract
Culture filtrate protein 10 (CFP-10) fromMycobacterium tuberculosisis a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells fromM. tuberculosis-infected mice and humans. The sequence of theMycobacterium lepraehomologue of CFP-10 shows only 40% identity (60% homology) at the protein level withM. tuberculosisCFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against recombinantM. lepraeandM. tuberculosisCFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for eitherM. lepraeorM. tuberculosisCFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell hybridomas raised against eitherM. lepraeorM. tuberculosisCFP-10 displayed a cross-reactive response against the N-terminal heterologous CFP-10 peptide, the region that exhibits the highest level of identity in the two proteins; however, the majority of peptide epitopes recognized by mouse T-cell hybridomas specific for each protein did not cross-react with heterologous peptides. Coupled with the human serology data, these results raise the possibility that peptides that could be used to differentiate infections caused by these two related microorganisms could be developed. Immunohistochemical staining of sections ofM. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting thatM. lepraeCFP-10, like its homologue inM. tuberculosis, is a secreted protein.