Biology and pathophysiology of MAIT cells in a new MAIT-rich wild-derived congenic mouse strain. Mus musculus

Despite the strong evolutionary conservation of the invariant TCRa chain and MR1 restricting molecule, MAIT cells (MAITs) are very abundant in humans (5-10% in blood) but rare in laboratory mouse strains (~0.1% in lymphoid organs).Lack of an appropriate mouse model hampers the study of MAIT biology.Herein, we show that MAITs are 20-times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57Bl/6J.This was linked to one CAST genetic trait that was mapped to the TCRa locus and led to higher usage of the distal Va segments (including Va19 used by MAITs) in CAST/EiJ.A "MAIThi" congenic strain was generated and crossed to a Rorc(gt)-GfpTG reporter strain.Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+), CD4-CD8low/neg T-cells with tissue-homing properties (CCR6+CCR7-).Similarly to human counterparts, mouse MAITs expressed the cytokine receptors, IL-7R, IL-18Ra and IL-12Rb and the transcription factors PLZF and RORgt.MAITs produced Th1/2/17 cytokines upon TCR stimulation and reacted towards a bacterial compound in an MR1-dependent manner.During an experimental urinary tract infection, MAITs migrated to the bladder and their presence decreased bacterial load.Thus, the "MAIThi" congenic strain allows the phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.