Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality worldwide. Effective host immunity is critical by sampling intracellular microbes and activating appropriate T cell responses through multiple antigen presentation pathways. This dissertation investigates how the immune system samples and presents Mtb-derived antigens, with a focus on MHC class I-related (MR1)-mediated antigen presentation and mucosal-associated invariant T (MAIT) cell responses. Specifically, this work elucidates mechanisms of MR1-mediated presentation of Mtb, MAIT cell functional plasticity, and identify host immune pathways that may be leveraged for therapeutic and vaccine strategies against tuberculosis.
