MAIT cells and microbial immunity

Abstract

Mucosal-associated invariant T (MAIT) cells, the most abundant T-cell subset in humans, are increasingly being recognized for their importance in microbial immunity. MAIT cells accumulate in almost every mucosal tissue examined, including the lung, liver and intestinal tract, where they can be activated through T-cell receptor (TCR) triggering as well as cytokine stimulation in response to a host of microbial products. In this review, we specifically discuss MAIT cell responses to bacterial and fungal infections, with a focus on responses that are both MR1-dependent and -independent, the evidence for diversity in MAIT TCR usage in response to discrete microbial products, protective immunity induced by MAIT cells, and MAIT cell antimicrobial functions in the context of these infections.

Keywords: MAIT cells; MR1; antimicrobial responses; infection; mucosal immunology; unconventional T cells.

Figure 1. The Intracellular Pathway of MHC Class I (MHC I)-Related Protein 1 (MR1) Ligand Presentation

MR1 is synthesized in the endoplasmic reticulum (ER) and passes through the Golgi where it either goes directly to the plasma membrane or remains in an intracellular vesicle. Whether an endogenous ligand (yellow) facilitates MR1 egress from the ER is not known. Exogenous MR1-ligands, such as 6-formyl pterin (FP) (purple) or those from an extracellular infection (orange), traverse the cell membrane and are loaded onto MR1 in the ER. MR1 at the plasma membrane may recycle back into the cytoplasm via recycling endosomes. MR1 vesicles may then be loaded with antigens from intracellular infection (pink) or from sampling extracellular infection and then translocate to the plasma membrane. It is also possible that some MR1 ligands from intracellular infections are transported to the ER via an unknown mechanism and are then loaded onto MR1.