MR1 antigen presentation to MAIT cells and other MR1-restricted T cells

MHC antigen presentation plays a fundamental role in adaptive and semi-invariant T cell immunity. Distinct MHC molecules bind antigens that differ in chemical structure, origin and location and present them to specialized T cells. MHC class I-related protein 1 (MR1) presents a range of small molecule antigens to MR1-restricted T (MR1T) lymphocytes. The best studied MR1 ligands are derived from microbial metabolism and are recognized by a major class of MR1T cells known as mucosal-associated invariant T (MAIT) cells. Here, we describe the MR1 antigen presentation pathway: the known types of antigens presented by MR1, the location where MR1-antigen complexes form, the route followed by the complexes to the cell surface, the mechanisms involved in termination of MR1 antigen presentation and the accessory cellular proteins that comprise the MR1 antigen presentation machinery. The current road map of the MR1 antigen presentation pathway reveals potential strategies for therapeutic manipulation of MR1T cell function and provides a foundation for further studies that will lead to a deeper understanding of MR1-mediated immunity. The MHC class I-related protein 1 (MR1) presents specific small molecule antigens to MR1-restricted T (MR1T) lymphocytes. These cells play an important role in infection and cancer, and strategies to target these cells are of considerable therapeutic interest. In this Review, McWilliam and Villadangos provide a comprehensive description of the antigen presentation pathway of MR1, which is fundamental for the understanding of MR1-mediated immunity and the potential therapeutic manipulation of MR1T cells.