Mucosal-associated invariant T (MAIT) cells are a subset of T-cells restricted by the MHC-related protein 1 (MR1). In mammals, MR1 is expressed in a variety of alternatively spliced isoforms. However, only the full-length transcript (MR1A) is conserved across species. In humans, three isoforms; MR1A, MR1B/D and MR1C are ubiquitously transcribed. MR1A is the most well characterised isoform and resembles classical MHC class I proteins, comprised of a heavy chain made of three extracellular domains, a transmembrane domain and a short cytoplasmic tail as well as β2-microglobulin. Whilst MR1B/D encodes for a truncated membrane bound protein lacking the α3-domain and MR1C encodes for a soluble protein. It has recently been shown that MR1A has the capacity to present riboflavin (vitamin B2) and folate (vitamin B9) derivatives as antigens. In contrast, less is known about the function of the other isoforms. Cell-line experiments by Lion et al, suggest that like MR1A, MR1B/D translocates to the cell surface following bacterial infection and activates MAIT cells. Thus, MR1B/D may act as an antigen-presenting molecule although presented antigens and antigen presentation pathways may be distinct. Alternatively, one could speculate that these isoforms may have distinct immunological functions. For example, excision of exon 5 in HLA class I molecules results in a secreted protein theorised to provide tolerance by binding to T-cell receptors. To address the physiological role of alternative splice forms of MR1, the relative expression of alternative splice forms in various human cell types and tissues will be assessed at the transcriptional and translational levels. We will also determine their cellular fate by western blot and immunofluorescence in comparison to MR1A and finally their role in MAIT cell activation by bacteria and synthetic antigens using a panel of cell lines generated to express the individual splice variants or combinations thereof.