Characterization of T-cell immunogenicity of two PE/PPE proteins of Mycobacterium tuberculosis

Chaitra, MG and Shaila, MS and Nayak, R (2008) Characterization of T-cell immunogenicity of two PE/PPE proteins of Mycobacterium tuberculosis. In: Journal of Medical Microbiology, 57 (9). pp. 1079-1086.

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Abstract

The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic variation among different strains of this bacterium. Two of the $PE\_PGRS$ protein-encoding genes, rv3812 and rv3018c, are expressed in pathogenic mycobacteria and are implicated, respectively, in the persistence of the organism in macrophages and in virulence. Peptides derived from these proteins have been predicted to bind major histocompatibility complex (MHC) class I with high affinity on the basis of immunoinformatics analysis, suggesting a possible role for these proteins in antimycobacterial immunity. In the present work, using DNA constructs containing the rv3812 and rv3018c genes of M. tuberculosis, the immunogenicity of these proteins was demonstrated in BALB/c mice. Immunization with either DNA construct induced a significant number of $CD8^+-type$ T cells and a strong Th1-type response, with high gamma interferon $(IFN-\gamma)$ and low interleukin-4 responses. Three nonameric peptides of Rv3812 and two of Rv3018c elicited a strong T-cell response in an MHC-restricted manner. An epitope-specific response was demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of perforin and $IFN-\gamma$ production. Experimentally, these peptides bound with high affinity to $MHC H-2K^d$ and showed low dissociation rates of peptide–MHC complexes. This study suggests that the identified T-cell epitopes may contribute to immunity against tuberculosis if included in a vaccine.

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:	18 Oct 2008 07:23
Last Modified:	19 Sep 2010 04:51
URI:	http://eprints.iisc.ac.in/id/eprint/16140

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