MHC class I-related protein 1 (MR1) (MR1)

Mucosal-associated invariant T (MAIT) cells are a specialized population of innate-like T cells that recognize small molecule metabolites presented by the MHC class I-related protein 1 (MR1) (Kjer-Nielsen et al., Nature, 2012). While traditionally known for their role in detecting bacterial and fungal infections through vitamin B2 biosynthetic intermediates, MAIT cells are increasingly recognized for their role in tumor immunology and their ability to recognize tumor-associated metabolic changes (Gherardin et al., Science Immunology, 2018). The MR1-MAIT axis is a compelling target for cancer immunotherapy because MR1 is non-polymorphic, potentially allowing for off-the-shelf cellular therapies that are effective across diverse patient populations regardless of HLA type (Crowther et al., Nature, 2020). Therapeutic strategies under investigation include the use of synthetic MR1 ligands to modulate MAIT cell activity, as well as the development of MR1-restricted T-cell receptor (TCR) therapies and CAR-MAIT cells designed to target tumor-associated antigens (TAAs) (Yan et al., Molecular Cancer, 2020). These approaches leverage the natural tissue-homing abilities and rapid effector responses of MAIT cells to induce potent anti-tumor immunity (Dogra et al., Cancer Cell, 2020).

Other names

MHC class I-related gene proteinClass I MHC-related antigenMR1MAIT cell-MR1 axis

MR1 presents small molecule metabolites (typically vitamin B derivatives or tumor-derived metabolic signatures) to the T-cell receptor (TCR) of Mucosal-associated invariant T (MAIT) cells. This interaction triggers MAIT cell activation, leading to the release of cytotoxic granules such as perforin and granzymes, as well as pro-inflammatory cytokines like IFN-gamma and TNF-alpha, which mediate the lysis of target tumor cells (Kjer-Nielsen et al., Nature, 2012; Crowther et al., Nature, 2020).