Epitope specificity and isoforms of the mycobacterial 19-kilodalton antigen

D. P. Harris, H. M. Vordermeier, S. J. Brett, G. Pasvol, C. Moreno, J. Ivanyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)2963-2972
Number of pages10
JournalInfection and Immunity
Volume62
Issue number7
DOIs
Publication statusPublished - 01 Jul 1994

Keywords

  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial/biosynthesis
  • Antibody Specificity
  • B-Lymphocytes/immunology
  • Bacterial Proteins/immunology
  • Cross Reactions
  • Cytokines/biosynthesis
  • Epitopes/immunology
  • Genetic Variation
  • H-2 Antigens/genetics
  • Humans
  • Immunodominant Epitopes/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mycobacterium tuberculosis/immunology
  • Peptide Fragments/immunology
  • Sequence Homology, Amino Acid
  • Species Specificity
  • T-Lymphocytes/immunology

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