Evaluation of T-cell responses to peptides with MHC class I-binding motifs derived from PE_PGRS 33 protein of Mycobacterium tuberculosis

J Med Microbiol. 2007 Apr;56(Pt 4):466-474. doi: 10.1099/jmm.0.46928-0.


The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic variation among different strains of M. tuberculosis. One of the PE_PGRS proteins, Rv1818c, plays a role in the pathogenesis of mycobacterial infection and specifically influences host-cell responses to tuberculosis infection. Although little is known about these two classes of protein, an immunoinformatics approach has indicated the possibility of their participation in eliciting a major histocompatibility complex (MHC) class I-mediated immune response against tuberculosis, as peptides derived from Rv1818c are predicted to bind to MHC class I molecules with high affinity. In the present work, a DNA vaccine was constructed encoding the full-length Rv1818c protein of M. tuberculosis and its immunogenicity was analysed in BALB/c mice. Immunization with Rv1818c DNA induced a strong CD8+ cytotoxic lymphocyte and Th1-type response, with high levels of gamma interferon (IFN-gamma) and low levels of interleukin-4. Two nonameric peptides (Peptide(6-14) and Peptide(385-393)) from Rv1818c were identified by their ability to induce the production of IFN-gamma by CD8+ T cells in mice immunized with Rv1818c DNA. An epitope-specific response was demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of cytotoxic granules and IFN-gamma production. These peptides bound with high affinity to MHC H-2K(d) and showed low dissociation rates of peptide-MHC complexes. These results could form the basis for testing the identified T-cell epitopes of PE_PGRS proteins in the induction of protective immunity against M. tuberculosis challenge in the mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / immunology*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / immunology*
  • Spleen / cytology
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology
  • Vaccines, Synthetic / immunology


  • Antigens, Bacterial
  • Bacterial Proteins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • PE-PGRS protein, Mycobacterium
  • Tuberculosis Vaccines
  • Vaccines, Synthetic