Identification of <i>Mycobacterium tuberculosis</i>-specific genomic regions encoding antigens inducing protective cellular immune responses

Abstract

Comparative genomic studies have identified 11 regions of difference (RD1, RD4, RD5, RD6, RD7, RD9, RD10, RD11, RD12, RD13 and RD15) in <i>Mycobacterium tuberculosis</i> genome which are absent in all vaccine strains of <i>M. bovis</i> BCG. The proteins encoded by genes predicted in these RDs could be useful as protective vaccines and/or exacerbate the disease process by inducing cellular immune responses involved in protection and pathogenesis of tuberculosis. In our studies, by using pools of overlapping synthetic peptides covering the sequence of putative proteins encoded by genes predicted in each RD, we have determined the cellular immune responses in relation to antigen-induced proliferation and secretion of the protective Th1 cytokine IFN-g and the pathologic Th2 cytokine IL-10 by peripheral blood mononuclear cells of tuberculosis patients and healthy humans. It has been observed that peptides of RD1_pool induced the highest antigen-induced proliferation and IFN-g responses, whereas the peptides of RD12_pool and RD13_pool induced the highest IL-10 responses. Furthermore, addition of RD12_pool and RD13_pool to peripheral blood mononuclear cells (PBMCs) cultures inhibited the RD1_pool-induced secretion of IFN-g by PBMCs of healthy humans. These results suggest the relevance of RD1-encoded proteins in protection and RD12- and RD13-encoded proteins in pathogenesis of tuberculosis.