Natural Polymorphism of Mycobacterium tuberculosis and CD8 T Cell Immunity
Authors
Sutiwisesak, RujapakFaculty Advisor
Samuel BeharAcademic Program
Immunology and MicrobiologyUMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Doctoral DissertationPublication Date
2020-02-24Keywords
TBtuberculosis
immunity
CD8 T cells
polymorphisms
evolution
immune evasion
immunodomination
Immunity
Immunology of Infectious Disease
Molecular Biology
Metadata
Show full item recordAbstract
Coevolution 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.DOI
10.13028/pkvd-8z28Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31300Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/pkvd-8z28