Samuel BeharSutiwisesak, Rujapak2022-08-232022-08-232020-02-242020-04-0610.13028/pkvd-8z28https://hdl.handle.net/20.500.14038/31300Coevolution between Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, and the human host has been documented for thousands of years. Interestingly, while T cell immunity is crucial for host protection and survival, T cell antigens are the most conserved region of the Mtb genome. Hypothetically, Mtb adapts under immune pressure to exploit T cell responses for its benefit from inflammation and tissue destruction for ultimately transmission. EsxH, a gene encoding immunodominant TB10.4 protein, however, contains polymorphic regions corresponding to T cell epitopes. Here, I present two complementary analyses to examine how Mtb modulates TB10.4 for immune evasion. First, I use a naturally occurring esxH polymorphic clinical Mtb isolate, 667, to investigate how A10T amino acid exchange in TB10.4 affect T cell immunity. To verify and identify the cause of the immunological differences, I construct isogenic strains expressing EsxHA10T or EsxHWT. In combination with our recent finding that TB10.44-11-specific CD8 T cells do not recognize Mtb-infected macrophages, we hypothesize that TB10.4 is a decoy antigen as it distracts host immunity from inducing other potentially protective responses. I examine whether an elimination of TB10.44-11-specific CD8 T cell response leads to a better host protective immunity. The studies of in vivo infection and in vitro recognition in this dissertation aim to provide a better understanding of the counteraction between immune evasion and protective immunity.en-USCopyright is held by the author, with all rights reserved.TBtuberculosisimmunityCD8 T cellspolymorphismsevolutionimmune evasionimmunodominationImmunityImmunology of Infectious DiseaseMolecular BiologyDoctoral Dissertationhttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2074&context=gsbs_diss&unstamped=1https://escholarship.umassmed.edu/gsbs_diss/107617223802gsbs_diss/10760000-0001-9685-3662