Evaluation of T-cell responses to peptides with MHC class I-binding motifs derived from PE_PGRS 33 protein of Mycobacterium tuberculosis.
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.
Chaitra
M G
MG
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Shaila
M S
MS
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Nayak
R
R
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
D020816:Amino Acid Motifs; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology*; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C440642:PE-PGRS protein, Mycobacterium; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic