Genetically permissive recognition of adjacent epitopes from the 19-kDa antigen of Mycobacterium tuberculosis by human and murine T cells

D. P. Harris, H. M. Vordermeier, G. Friscia, E. Roman, H. M. Surcel, G. Pasvol, C. Moreno, J. Ivanyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The specificity of the T cell-immune repertoire at the level of individual antigenic determinants could play a fundamental role in the immunopathogenesis of tuberculous infections. Therefore, we analyzed the immunogenicity, genetic restriction, and epitope core structure of two adjacent, yet distinct, immunodominant T cell determinants from the 19-kDa Ag of Mycobacterium tuberculosis. After immunization with two peptides comprising residues 45 to 64 and 61 to 80, vigorous in vitro proliferate responses to the homologous peptide were elicited in five different strains of C57BL/10 mice(H-2 b,k,d,s,f), indicating that both epitopes were recognized in a genetically permissive manner. When immunized with intact 19-kDa protein, lymph node cells from the same mouse strains responded to both peptides, with the exception of H-2 b mice, which did not respond to p45-64. Delayed-type hypersensitivity responses in C57BL/10 (H-2 b) mice were elicited by p61-80 only, whereas in H-2 d mice both peptides were delayed-type hypersensitivity negative, despite eliciting pronounced proliferative responses. Analysis of the proliferative responses of human PBMC in purified protein derivative-positive healthy subjects and tuberculosis patients revealed significant differences in the antigenicity to the two peptides. All purified protein derivative-positive healthy and diseased individuals manifested strong responses to p45-64, indicating HLA permissive recognition. In contrast, pronounced responses to p61-80 were detected only in patients with lymphatic tuberculosis. Epitope core structures, composed of 6 or 7 residues within each peptide, have been mapped with peptides of overlapping sequence. Significantly, for both epitopes, the core sequences recognized by both human and murine T cells were almost identical. We conclude that despite many similarities between murine and human T cell epitope recognition, distinct differences in the responsiveness of the infected host could play a role in pathogenesis. Furthermore, the genetically permissive nature of the identified epitopes is a potentially important attribute for the development of peptide-based diagnostic reagents and vaccines.

Original languageEnglish
Pages (from-to)5041-5050
Number of pages10
JournalJournal of Immunology
Volume150
Issue number11
Publication statusPublished - 01 Jun 1993

Keywords

  • Adult
  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial/genetics
  • Female
  • H-2 Antigens/genetics
  • Humans
  • Hypersensitivity, Delayed/immunology
  • Immunodominant Epitopes/genetics
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Middle Aged
  • Molecular Sequence Data
  • Molecular Weight
  • Mycobacterium tuberculosis/genetics
  • T-Lymphocytes/immunology
  • Tuberculosis/immunology

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