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

Chaitra, MG and Shaila, MS and Nayak, R (2007) Evaluation of T-cell responses to peptides with MHC class I-binding motifs derived from PE_PGRS 33 protein of Mycobacterium tuberculosis. In: Journal of Medical Microbiology, 5 (4). pp. 466-474.

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Abstract

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 1-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 and low levels of interleukin-4. Two nonameric peptides (Peptides (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.

Item Type:	Journal Article
Publication:	Journal of Medical Microbiology
Publisher:	Society for General Microbiology
Additional Information:	Copyright of this article belongs to Society for General Microbiology.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	31 Jul 2007
Last Modified:	02 Feb 2012 07:04
URI:	http://eprints.iisc.ac.in/id/eprint/11630

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