Mucosal Associated Invariant T cells (MAIT) represent a key immune cell population because of their abundance in humans, their ability to provide immediate responses upon stimulation, and their potential involvement in many pathologies. MAIT cells recognize microbiota-derived metabolites presented by the MHC-related molecule MR1. Both MR1 and the TCR of MAIT cells are conserved in evolution, indicating non-redundant functions linked to antigen recognition. MAIT ligands produced by the microbiota control MAIT cell development. However, mechanisms underlying microbiota production of MAIT antigens remain undefined. Upon thymic egress, MAIT cells migrate to mucosal and liver tissues where they accumulate over time and reach high frequencies in humans (1-10% of T cells in the intestine, 20-45% in liver). MAIT cells are further recruited and activated in the intestinal lesions of patients with inflammatory bowel diseases, suggesting a role in these pathologies. Whether MAIT cell accumulation and function in intestinal tissues rely on the recognition of microbiota-derived antigens is unknown, and the role played by MAIT cells in the gut also remains unclear. The MicrobMAIT proposal aims at addressing the role played by microbiota-derived antigens in the biology of MAIT cells. We will take advantage of innovative genetic tools and reagents to: 1. Explore rules governing MAIT antigen production by the microbiota, in mice and humans 2. Determine the dynamics of MAIT antigens and identify antigen-presenting cells in vivo 3. Define the influence of the microbiota on MAIT cell maintenance and function during intestinal inflammation Based on our sound preliminary data, we expect to identify a new MAIT-dependent mechanism of immune surveillance of the intestinal microbiota. Future manipulation of this interaction may offer innovative therapeutic opportunities against intestinal inflammation as well as colonic carcinogenesis.