The burgeoning role of MR1-restricted T-cells in infection, cancer and autoimmune disease.

MR1-restricted T-cells (MR1Ts) encompass an ever increasing range of T-cells. MR1T can represent ∼10% of total T-cells with the vast majority of these being mucosal-associated invariant T (MAIT) cells which recognise microbial metabolites, canonically intermediates in riboflavin biosynthesis via a TRAV1.2 semi-invariant T-cell receptor, although noncanonical MAITs have been described. Furthermore, MR1T cells have been identified that recognise self-antigens presented by monocyte-derived DCs, and MC-7.G5-like cells that recognise cancer. [Display omitted] • MR1 is an evolutionarily conserved antigen presentation platform. • MR1 presents endogenous and bacterial metabolite ligands to T-cells. • Recent data shows MR1-restricted T-cells may play important roles in cancer. • The conserved nature of MR1 may allow pan-population therapies for many diseases. MR1 is a ubiquitously expressed, monomorphic antigen presenting molecule that has been largely preserved throughout mammalian evolution. The primary role of MR1 is to present conserved microbial metabolites to highly abundant mucosal-associated invariant T (MAIT) cells. The role of MAIT cells and other MR1-restricted T cells (MR1T) has been recently extended to immunomodulation during cancer. MR1Ts have also been implicated in autoimmune disease. The highly conserved nature of MR1 across the human population is in stark contrast to the MHC molecules recognised by conventional αβ T-cells, therefore MR1Ts may form fertile ground for the development of pan-population T-cell immunotherapeutics for a wide range of important morbidities. [ABSTRACT FROM AUTHOR]