Mucosal-associated invariant T-cell receptor (MAIT TCR) (MAIT TCR)

The Mucosal-associated invariant T-cell receptor (MAIT TCR) is a specialized T-cell receptor characterized by a semi-invariant alpha chain (typically TRAV1-2 joined to TRAJ33/12/20 in humans) paired with a restricted set of beta chains (Kjer-Nielsen et al., Nature, 2012). Unlike traditional T-cell receptors that recognize peptide antigens presented by MHC molecules, the MAIT TCR specifically recognizes small-molecule metabolites derived from the riboflavin biosynthesis pathway, such as 5-OP-RU, presented by the highly conserved MHC-related protein 1 (MR1) (Corbett et al., Nature, 2014). MAIT cells are highly prevalent in mucosal tissues and the liver, where they serve as a bridge between innate and adaptive immunity by rapidly responding to bacterial and fungal pathogens (Toubal et al., Nature Reviews Immunology, 2019). Activation of the MAIT TCR leads to the production of pro-inflammatory cytokines like IFN-gamma and IL-17, as well as the release of cytotoxic granules to eliminate infected or transformed cells (Gherardin et al., Nature Communications, 2016). Because of its role in both protective immunity and pathological inflammation, the MAIT TCR is an emerging therapeutic target for infectious diseases, cancer immunotherapy, and autoimmune disorders (Keller et al., Frontiers in Immunology, 2017).

Other names

MAIT receptorSemi-invariant T-cell receptorTRAV1-2-containing TCRMR1-restricted T-cell receptor

Agonist ligands bind to the MR1 protein, which presents the metabolite to the MAIT TCR, triggering T-cell activation and the release of pro-inflammatory cytokines and cytotoxic molecules. Antagonists competitively bind MR1 to prevent TCR-mediated activation.