Environmental regulation of mucosal-associated invariant T cells: Adding food for thought

Mucosal-associated invariant T (MAIT) cells are a population of innate-like, unconventional T cells characterized by the expression of a semi-invariant, non-MHC-restricted T cell receptor (TCR), which play an important role in mediating innate immune responses to bacterial and viral pathogens. Emerging research continues to describe the many environmental signals that influence the types of responses elicited downstream of MAIT cell activation. In this Review, we highlight five key factors that determine the metabolic and functional responses of MAIT cells, including TCR engagement, costimulation, chemokine signaling, cytokine stimulation, and nutrient availability. We further define the importance of optimal nutrient availability as "signal 5" in promoting MAIT cell fitness and in governing their capacity to respond appropriately to challenge. In understanding the ways in which MAIT cells are influenced by their microenvironment, we can continue to identify the potential factors that drive dysregulated responses in hostile circumstances, enabling restoration of their protective nature in the context of infection or in the tumor microenvironment.