Mucosal Associated Invariant T cells Respond in vivo to Riboflavin-derived Ligands and Co-stimulatory Signals

We have analysed the requirements for triggering Mucosal Associated Invariant T (MAIT) cell responses in a mouse model. MAIT cells are a subset of non-conventional T cells, which are restricted by the MHC Class I related (MR1) molecule. Although they have been implicated in the immune response to certain bacteria, their overall role in infection remains unclear. Having recently identified the antigens recognized by these cells as small ring compounds deriving from riboflavin biosynthesis precursors, we now aim to explore the activation and response of MAIT cells in mucosal infection. Here we use an intranasal infection model with gene-deleted mutant bacteria to confirm the requirement for riboflavin-derived ligands in triggering MAIT cells. We also characterize the phenotype, cytokine production and co-receptor expression of responding cells, and show that a full response requires both specific recognition of antigen and co-stimulatory signals.