title: A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.
abstract: Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: V
authors.initials: V
authors.lastname: Mehra
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
authors.forename: A C
authors.initials: AC
authors.lastname: Bajardi
authors.forename: C L
authors.initials: CL
authors.lastname: Grisso
authors.forename: P A
authors.initials: PA
authors.lastname: Sieling
authors.forename: D
authors.initials: D
authors.lastname: Alland
authors.forename: J
authors.initials: J
authors.lastname: Convit
authors.forename: X D
authors.initials: XD
authors.lastname: Fan
authors.forename: S W
authors.initials: SW
authors.lastname: Hunter
authors.forename: P J
authors.initials: PJ
authors.lastname: Brennan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D001135:Armadillos; D015153:Blotting, Western; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007918:Leprosy / Q000276:immunology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; C072209:major T cell antigen, Mycobacterium leprae