Mucosal-associated invariant T (MAIT) cells are highly enriched in the lung and play a key role in early immune defense against a broad array of pathogens, including mycobacteria. MR1 is a Class I-related molecule that presents metabolites of the riboflavin synthesis pathway to activate MAIT cells. MR1 is unusual amongst MHC molecules as MR1 pre-mRNA undergoes alternative splicing to produce multiple isoforms. Only the full length isoform, MR1A, is known to activate MAIT cells. The other isoforms, MR1B and MR1C, are not well characterized, although MR1B is thought to activate MAIT cells. 

To test the function of MR1 isoforms, we transfected MR1-deficient A549 cells with plasmids expressing each of the MR1 isoforms.  We then infected these cells with M. smegmatis and tested their ability to activate MAIT cells.  Cells expressing MR1A activated MAIT cells, but neither MR1B nor MR1C could do so. When coexpressed with MR1A, MR1B inhibited MAIT cell activation following infection. We further show that MR1A and MR1B colocalize inside intracellular vesicles. We hypothesize that MR1B prevents MR1A loading with ligand or trafficking to the cell surface. These data suggest that MR1A mediated activation of MAIT cells may be regulated by MR1B, thereby avoiding inappropriate MAIT cell activation in the absence of mycobacterial infection.