Chaitra, M. G. ; Shaila, M. S. ; 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 Journal of Medical Microbiology, 56 (4). pp. 466-474. ISSN 0022-2615
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Official URL: http://jmm.sgmjournals.org/content/56/4/466.abstra...
Related URL: http://dx.doi.org/10.1099/jmm.0.46928-0
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 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-γ) and low levels of interleukin-4. Two nonameric peptides (Peptide6-14 and Peptide385-393) from Rv1818c were identified by their ability to induce the production of IFN-γ 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-γ production. These peptides bound with high affinity to MHC H-2Kd 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: | Article |
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Source: | Copyright of this article belongs to Society for General Microbiology. |
ID Code: | 49351 |
Deposited On: | 20 Jul 2011 06:19 |
Last Modified: | 20 Jul 2011 06:19 |
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