Abstract
Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they must fulfill critical immunological function(s). MAIT cells are defined by their expression of a semi-invariant αβ TCR which recognizes biosynthetic derivatives of riboflavin synthesis presented on MR1. Initial studies focused on their role in detecting predominantly intracellular bacterial and mycobacterial infections. However, it is now recognized that there are several modes of MAIT cell activation and these are related to activation of distinct transcriptional programmes, each associated with distinct functional roles. In this minireview, we summarize current knowledge from human and animal studies of MAIT cell activation induced (1) in an MR1-TCR dependent manner in the context of inflammatory danger signals and associated with antibacterial host defense; (2) in an MR1-TCR independent manner by the cytokines interleukin(IL)-12/-15/-18 and type I interferon, which is associated with antiviral responses; and (3) a recently-described TCR-dependent “tissue repair” programme which is associated with accelerated wound healing in the context of commensal microbiota. Because of this capability for diverse functional responses in diverse immunological contexts, these intriguing cells now appear to be multifunctional effectors central to the interface of innate and adaptive immunity.
Highlights
Mucosal-associated invariant T (MAIT) cells are innate-like T cells defined by their semi-invariant αβ T cell receptor (TCR) which recognizes small-molecule biosynthetic derivatives of riboflavin synthesis [1,2,3] presented on the restriction molecule major histocompatibility complex (MHC)-related protein-1 (MR1) [4]
MAIT cells contrast with conventional T cells which have highly variable TCRs, capable of targeting a vast array of peptide epitopes produced by viruses, bacteria and malignant cells
MAIT cells are abundant in the normal airway mucosa, but we have shown frequencies are markedly reduced by therapeutic corticosteroids in both asthma [18] and chronic obstructive pulmonary disease (COPD) [19]
Summary
Mucosal-associated invariant T (MAIT) cells are innate-like T cells defined by their semi-invariant αβ T cell receptor (TCR) which recognizes small-molecule biosynthetic derivatives of riboflavin synthesis [1,2,3] presented on the restriction molecule major histocompatibility complex (MHC)-related protein-1 (MR1) [4]. We review both the mechanisms and requirements for MAIT cell activation, and our current understanding of their diverse functional roles, including response to bacterial infections, viral infections and tissue repair.
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