1887

Abstract

The PE and PPE proteins of form a source of antigenic variation among different strains of . 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 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-) and low levels of interleukin-4. Two nonameric peptides (Peptide and Peptide) from Rv1818c were identified by their ability to induce the production of IFN- 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- production. These peptides bound with high affinity to MHC H-2K 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 challenge in the mouse model.

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2007-04-01
2020-09-19
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