In silico identification of potential antigenic proteins and promiscuous CTL epitopes in Mycobacterium tuberculosis

Cell-mediated immunity is critical for the control of Mycobacterium tuberculosis infection. We hypothesized that those proteins of M. tuberculosis (MTB) that do not have homologs in humans as well as human gut flora, would mount a good antigenic response in man, and employed a bioinformatics approach to identify MTB antigens capable of inducing a robust cell-mediated immune response in humans. In the first step we identified 624 MTB proteins that had no homologs in humans. Comparison of this set of proteins with the proteome of 77 different microbes that comprise the human gut flora narrowed down the list to 180 proteins unique to MTB. Twenty nine of the 180 proteins are known to be associated with dormancy. Since dormancy associated proteins are known to harbor CTL epitopes, we selected four representative unique proteins and subjected them to epitope analysis using ProPred1. Nineteen novel promiscuous epitopes were identified in the four proteins. Population coverage for 7 of the 19 shortlisted epitopes including Rv3852 (58-KPAEAPVSL, 112-VPLIVAVTL, 118-VTLSLLALL and 123-LALLLIRQL), Rv2706c (66-RPLSGVSFL) Rv3466 (8- RIVEVFDAL and 38-RSLERLECL) was >74%. These novel promiscuous epitopes are conserved in other virulent MTB strains, and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates.