FUNCTIONS AND SPECIFICITY OF T-CELLS FOLLOWING NUCLEIC-ACID VACCINATION OF MICE AGAINST MYCOBACTERIUM-TUBERCULOSIS INFECTION

The 38-kDa glycolipoprotein of Mycobacterium tuberculosis has been kno wn to evoke prominent T cell and Ab responses in patients with active tuberculosis, In this study, we investigated its protective capacity u sing plasmid DNA immunization in a mouse experimental model, Prior kno wledge of several antigenic determinants has been beneficial for analy zing the phenotype and specificity of T cells, which determine the eff icacy of this vaccination procedure, C57BL/6 mice responded to the 38- kDa gene-pcDNA3 plasmid with strong CD4(+) Th1 and CD8(+) cytotoxic T cell responses of the IFN-gamma-producing Tc1 phenotype, After challen ge with virulent tubercle bacilli, the bacterial load in the spleens a nd lungs of vaccinated mice was reduced to a level similar to that imp arted by Mycobacterium bovis Bacille Calmette-Guerin vaccination. Nota bly, the specificity of CD4(+) and CD8(+) T cells from DNA-vaccinated and tubercle-infected mice was found to be strikingly different in res pect of several peptide epitopes, The identified peptides recognized b y T cells from protected mice are of further interest for the developm ent of subunit-based vaccines against tuberculosis.