title: Cell envelope protein PPE68 contributes to Mycobacterium tuberculosis RD1 immunogenicity independently of a 10-kilodalton culture filtrate protein and ESAT-6.
abstract: The protective efficacy of Mycobacterium bovis BCG can be markedly augmented by stable integration of Mycobacterium tuberculosis genomic region RD1. BCG complemented with RD1 (BCG::RD1) encodes nine additional proteins. Among them, 10-kDa culture filtrate protein (CFP-10) and ESAT-6 (6-kDa early secreted antigenic target) are low-molecular-weight proteins that induce potent Th1 responses. Using pools of synthetic peptides, we have examined the potential immunogenicity of four other RD1 products (PE35, PPE68, Rv3878, and Rv3879c). PPE68, the protein encoded by rv3873, was the only one to elicit gamma interferon (IFN-gamma)-producing cells in C57BL/6 mice infected with M. tuberculosis. Anti-PPE68 T cells were predominantly raised against an epitope mapped in the N-terminal end of the protein. Importantly, inactivation of rv3873 in BCG::RD1 did not modify CFP-10 and ESAT-6 secretion. Moreover, the generation of IFN-gamma responses to these antigens following immunization with BCG::RD1 was independent of PPE68 expression. Taken together, these results show that PPE68 is an immunogenic product of the RD1 region, which does not interfere with the secretion and immunogenicity of CFP-10 and ESAT-6.
authors.affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 75724 Paris Cedex 15, France. demangel@pasteur.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Demangel
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cockle
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007371:Interferon-gamma