Genetic diversity of antigens Rv2945c and Rv0309 in Mycobacterium tuberculosis strains may reflect ongoing immune evasion.

Host immune pressure and associated immune evasion of pathogenic bacteria are key features of host-pathogen co-evolution. A previous study showed that human T-cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 173 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the genes encoding Rv2945c and Rv0309, and compared the sequences. The results showed that genetic diversity existed in these two genes among the MTBC strains and two single nucleotide polymorphisms (SNPs) presented higher polymorphisms. Antigen Rv2945c harbored a higher number of amino acid substitutions of its T-cell epitopes, which may reflect ongoing immune evasion. In addition, the high dN/dS value of Rv0309 suggested antigen Rv0309 might be involved in diversifying selection to evade host immunity. Finally, a small group of strains were identified based on the genetic diversity of these two genes, which might indicate that they interact differently with human T cells compared with other strains.