Mining the Mycobacterium tuberculosis proteome for identification of potential T-cell epitope based vaccine...

Identification of protective antigens for designing a high-efficacy tuberculosis vaccine is the need of the hour. Till date only 7% of the Mycobacterium tuberculosis proteome has been explored for discovering antigens capable of activating T-cell responses. Therefore, it becomes crucial to screen the remaining Mycobacterium tuberculosis proteome for more immunodominant T-cell epitopes. An extensive knowledge of the epitopes recognized by our immune system can aid this process of finding potential T cell antigens for development of a better TB vaccine. In the present in-silico study, 237 proteins belonging to the 'virulence, detoxification, and adaptation' category of Mycobacterium tuberculosis proteome were targeted for T-cell epitope screening. 50825 MHC Class I and 49357 MHC Class II epitopes were generated using NetMHC3.4 and IEDB servers respectively and tested for their antigenicity and cytokine stimulation. The highest antigenic epitopes were analyzed for their world population coverage and epitope conservancy. Molecular docking and molecular dynamics simulation studies were performed to corroborate the binding affinities and structural stability of the peptide-MHC complexes. We predicted a total of 3 MHC Class I (ILLKMCWPA, FAVGMNVYV, and SLAGNSAKV) and 7 MHC Class II (DLTIGFFLHIPFPPV, RPDLTIGFFLHIPFP, LTIGFFLHIPFPPVE, VLVFALVVALVYLQF, LVFALVVALVYLQFR, PNLVAARFIQLTPVY, and LVLVFALVVALVYLQ) epitopes that can be promising vaccine candidates. These predicted epitopes belong to 6 distinct proteins: Rv0169 (mce1a), Rv3490 (ostA), Rv3496 (mce4D), Rv1085c, Rv0563 (HtpX), Rv3497c (mce4C). All these proteins are expressed at different stages in the life cycle of Mycobacterium tuberculosis and thus, the predicted epitopes could be employed as candidates for designing a multistage-multiepitopic vaccine.