The study investigates the anti-microbial activity of Mucosal Associated Invariant T (MAIT) cells, which are characterized by an invariant TCRα chain and restriction by the MHC-related protein MR1. MAIT cells are activated by bacteria and yeasts but not viruses, both in humans and mice. This activation requires interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, MAIT cell numbers are significantly reduced in patients with bacterial infections such as tuberculosis. In mice, MAIT cells protect against infections by *Mycobacterium* and *Escherichia coli*. The results suggest that MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infections.The study investigates the anti-microbial activity of Mucosal Associated Invariant T (MAIT) cells, which are characterized by an invariant TCRα chain and restriction by the MHC-related protein MR1. MAIT cells are activated by bacteria and yeasts but not viruses, both in humans and mice. This activation requires interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, MAIT cell numbers are significantly reduced in patients with bacterial infections such as tuberculosis. In mice, MAIT cells protect against infections by *Mycobacterium* and *Escherichia coli*. The results suggest that MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infections.