Background: Mucosal-Associated Invariant T-cells (MAIT cells) are innate T-cells that recognize microbial antigens presented by MHC class I-related (MR1) molecules. Despite ubiquitous expression of MR1 and recent breakthroughs in understanding MAIT cell biology, the antigen presenting cells (APCs) that drive MAIT cell activation remain poorly characterized.

Methods: Using different in-vitro and in-vivo models, we provide a comprehensive analysis of the role of different APCs in MAIT cell activation.

Results: Dendritic cells (DCs) and macrophages efficiently present antigens to MAIT cells, while  B-cells do not. Additionally, stimulation of MAIT cells with antigen-loaded DCs resulted in greater proliferation of MAIT cells compared to macrophages. Moreover, higher cytokine secretion was noted in combined TLR/antigen stimulation in DC/T-cell co-cultures compared to stimulation with antigen or TLR alone. While only a modest increase was noted in similar macrophage/T-cell co-cultures. Notably, depletion of DCs/macrophages caused reduction in MAIT cell expansion, but depletion of B-cells had an opposite effect. Furthermore, adoptive transfer ofantigen-loaded BMDCs/BMDMs into wild-type mice recapitulated our in-vitro findings.

Conclusions: Various APCs differ in their abilities to activate MAIT cells with DCs being most potent. These findings suggest that APC- targeted approaches to MAIT cell activation may open novel avenues for therapeutic manipulation of MAIT cells.