The low number of MAITs in laboratory mice is puzzling given the high number of these cells in humans and the striking evolutionary conservation of the invariant TCR and MR1-restricting MHC molecule.

We show that the low number of MAITs in mice is linked to one genetic trait that has probably been lost during the establishment of laboratory mice. The Castaneus strain harbors 20 times more MAITs in the periphery than C57Bl/6 mice. This was mapped to the TCRa locus with a chromosome intrinsic higher usage of the most distal Va segments, which includes the Va19 segment used by MAITs.  A "MAIT" congenic B6 strain was generated and further crossed to a Rorc(gt)-GFP reporter allowing us to track MAITs as memory GFP⁺DN-CD8^lo T cells.

Polyclonal mouse MAITs are memory (CD44⁺) with tissue-homing properties (CCR6⁺CCR7^-). As in humans, mouse MAITs express IL-7R, IL-18Ra and IL-12Rb and, PLZF and RORgt. MAITs produce Th1/2/17 cytokines and are stimulated by MR1-overexpressing cells loaded with MAIT ligand. In this new mouse model polyclonal MAITs decreased bacterial load during an experimental urinary tract infection.

Although Riboflavin precursor derivatives from Gram+ bacteria have been characterized as the main MAIT ligands, some level of heterogeneity has been suggested. The study of Gram- bacteria mutated for the riboflavin biosynthesis pathway shows a strict correlation between the ability to synthesize 5-amino-ribityl-uracil and to activate mouse MAITs. Thus most if not all MAIT ligands found in E. Coli are related to the riboflavin biosynthesis pathway and display very limited heterogeneity.

In humans, blood MAIT frequency is modified in multiple sclerosis (increase), IBD (decrease), Type-2 diabetes and obesity (decrease), all diseases in which dysbiosis of the gut microbiota has been implicated. Thus, MAITs could be involved in the symbiotic feedback loops between gut microbiota, epithelial cells and immune cells.