title: Epitope specificity and isoforms of the mycobacterial 19-kilodalton antigen.
abstract: The topography and specificity of B- and T-cell stimulatory epitopes from the 19-kDa protein of Mycobacterium tuberculosis were investigated by using overlapping synthetic peptides. Murine antisera identified two cryptic epitopes (residues 11 to 30 and 61 to 80) and one species-specific immunodominant epitope (residues 140 to 159). Immunoglobulins G1 and G2a antibody isotypes varied for the respective peptide immunogens but without relationship to the T-cell cytokine profiles which were characterized by high gamma interferon and low interleukin 5 levels. Antisera to recombinant M. tuberculosis 19-kDa protein (rGST-19) cross-reacted with homologous proteins of similar size from organisms of the Mycobacterium avium-intracellulare complex. Two-dimensional gel electrophoresis revealed differences in the number, relative mobility, and charge of isoforms of the 19-kDa protein, possibly reflecting posttranslational modifications. The immunodominant T-cell epitope from the M. tuberculosis 19-kDa protein (residues 61 to 80) and the corresponding peptide sequence from Mycobacterium avium subsp. intracellulare (residues 64 to 83), differing at five residues, were both recognized in a genetically permissive manner. Peptides 61-80 and 64-83 stimulated cross-reactive responses in BALB/c (H-2d) mice, while in the C57BL/10 (H-2b) strain, responses to peptide 61-80 were species specific. In purified protein derivative-positive healthy individuals, the M. avium subsp. intracellulare peptide stimulated stronger responses than did the M. tuberculosis peptide, whereas patients with active tuberculosis had enhanced in vitro T-cell responses to both peptides.
authors.affiliation: MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: D P
authors.initials: DP
authors.lastname: Harris
authors.forename: H M
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: S J
authors.initials: SJ
authors.lastname: Brett
authors.forename: G
authors.initials: G
authors.lastname: Pasvol
authors.forename: C
authors.initials: C
authors.lastname: Moreno
authors.forename: J
authors.initials: J
authors.lastname: Ivanyi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C087864:19 kDa antigen, Mycobacterium; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D000939:Epitopes; D006183:H-2 Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments