Mucosal-associated invariant T cell (MAIT cell)

Mucosal-associated invariant T (MAIT) cells are a specialized subset of innate-like T lymphocytes that bridge the innate and adaptive immune systems [1, 16]. They are defined by a semi-invariant T-cell receptor (TCR), typically Vα7.2-Jα33 in humans, which recognizes small molecule metabolites presented by the non-polymorphic MHC class I-related protein 1 (MR1) [11, 15]. These metabolites, such as 5-OP-RU, are primarily derived from the riboflavin (vitamin B2) biosynthesis pathway found in many bacteria and fungi [8, 10]. MAIT cells are highly abundant in human mucosal tissues and the liver, where they provide rapid effector functions, including the production of pro-inflammatory cytokines like IFN-γ and TNF-α, and direct cytotoxicity against infected or malignant cells [2, 14]. In therapeutic development, MAIT cells are being explored as targets for small molecule modulators to treat infections and autoimmune diseases, and as a versatile platform for 'off-the-shelf' chimeric antigen receptor (CAR) cell therapies due to their non-alloreactive nature [3, 6].

Other names

MAIT cellsMR1-restricted T cellsMucosal-associated invariant T-cells

Drugs modulate MAIT cell activity by binding to the MR1 protein, which presents these ligands to the semi-invariant T-cell receptor (TCR). Agonistic ligands (e.g., 5-OP-RU) trigger TCR signaling, leading to cytokine production and cytotoxicity, while antagonistic ligands (e.g., 6-FP) block this interaction. MAIT cells can also be activated independently of the TCR via cytokine-mediated pathways involving IL-12 and IL-18.