Major histocompatibility complex class I-related gene protein (MR1) (MR1)

Major histocompatibility complex class I-related gene protein (MR1) is a non-polymorphic, MHC class I-like molecule essential for the activation of Mucosal-associated invariant T (MAIT) cells (UniProt Q95460). Unlike traditional MHC molecules that present peptides, MR1 captures and presents small-molecule metabolites, primarily those derived from the riboflavin (vitamin B2) biosynthetic pathway found in various bacteria and fungi (Corbett et al., Nature 2014). This unique presentation mechanism allows the immune system to detect microbial infections through metabolic signatures rather than protein sequences. MR1 is highly conserved across species, meaning it does not exhibit the high degree of polymorphism seen in classical HLA molecules, which makes it a "universal" target for all individuals (Kjer-Nielsen et al., Nature 2012). In addition to its role in infectious disease, MR1 has gained significant interest in cancer immunotherapy following the discovery of MR1-restricted T cells that can recognize and eliminate diverse tumor types in an MHC-independent manner (Crowther et al., Nature Immunology 2020). Therapeutic strategies currently under investigation include the use of synthetic MR1 ligands to either activate or inhibit MAIT cell responses in the context of infection, autoimmunity, and malignancy (Keller et al., Scientific Reports 2017).

Other names

Major histocompatibility complex-related molecule 1MHC class I-related gene proteinMR1HLALS

MR1 binds small-molecule metabolites (ligands) in its antigen-binding cleft and presents them to the T-cell receptor (TCR) of Mucosal-associated invariant T (MAIT) cells, leading to T-cell activation and effector functions (Corbett et al., Nature 2014).