AbstractIn humans, MAIT cells represent the most abundant T‐cell subset reacting against bacteria. MAIT cells belong to the evolutionarily conserved family of “preset” T cells that includes also NKT cells. Both subsets are selected by double positive thymocytes leading to common features such as PLZF expression. Preset T cells correspond to subsets prepositioned in specific tissue locations with preprogrammed versatile effector functions such as antimicrobial functions and possibly also metabolic control and tissue repair activity. Herein, we recall how several groups studying human samples discovered MAIT cells as T cells expressing either a restricted T‐cell receptors (TCR) repertoire or homogeneous and singular phenotypic and functional characteristics. We then highlight the main evolutionary features of this subset and its restricting element, MR1 (MHC‐related protein (1) with a striking coevolution of TRAV1 and MR1. We introduce another evolutionarily conserved invariant TCRalpha chain coevolving with another MHC class Ib molecule, called MHX, sharing phylogenetic features with MR1. We finally discuss the relationship between MAIT cells and other subsets reacting to microbial antigens or to compounds presented by MR1 in light of confounding experimental issues.