Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. Upon activation, MAIT cells are capable of immediate effector function, releasing cytotoxic molecules and pro-inflammatory cytokines in mucosal tissue. MAIT cells are restricted by the MHC class I-related molecule MR1, which presents non-protein antigens such as small molecule metabolites generated as byproducts of microbial riboflavin biosynthesis. At rest, MR1 proteins primarily reside in the ER or endosomal compartments. Ligand-bound MR1 translocates to the cell surface through distinct trafficking mechanisms for presentation of antigens from intracellular and extracellular pathogens. The abundance of both MAIT cells and putative antigen sources in the mucosal periphery necessitates strict control of MR1 antigen presentation to avoid inappropriate MAIT cell activation. These studies characterize novel regulatory mechanisms of MR1 transcriptional expression, endosomal trafficking, and recycling pathways. Dysregulation of these pathways in the context of environmental toxins like cigarette smoke (CS) and inflammatory diseases like chronic obstructive pulmonary disease (COPD) leads to altered MR1 expression, dysfunctional MAIT cell activation, and pathogenic feed-forward inflammatory signaling cycles. Together, this work demonstrates that regulation of MR1 transcription and antigen presentation is critical to balance appropriate and proportional MAIT cell responses to respiratory insults.