Identification and characterization of proteome-wide T cell epitopes from Mtbin active tuberculosis infection

Abstract

Abstract Tuberculosis caused by Mycobacterium tuberculosis is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different states of tuberculosis (TB) infection can help in designing both diagnostics and vaccines. We performed proteome-wide screen of 21,220 Mtb derived peptides in 21 mid-treatment active TB patients using IFN-γ fluorospot assay. The overall breadth of IFN-γ responses in active TB recognized an average of 10 individual epitopes. In total, we identified 175 individual epitopes, and 37 of those (21.1%) were recognized by 2 or more individuals. These responses were predominantly directed against antigens part of the cell wall and cell processes category. We also found differential reactivity in active TB and LTBI cohorts in terms of clusters of antigens recognized and recognition of TB vaccine candidate antigens. Interestingly, we have identified 9 novel antigens, which have not been described as antigens for Mtb in the past. Additionally, we created a pool of peptides only recognized by individuals with active TB. This active-specific pool has shown higher T cell response in a new active TB cohort compared to individuals with LTBI suggesting a better pool for distinguishing these disease states. Therefore, identifying disease state-specific epitopes and antigens will help in the development of diagnostics, vaccine candidates and correlate of protection.