MHC I-related protein 1(MR1) is a monomorphic antigen-presenting molecule that presents vitamin B metabolites to mucosal-associated invariant T cells (MAIT cells). MAIT cells recognize these metabolite antigens presented by MR1, produced by a broad range of bacteria and yeast, and respond rapidly by killing infected cells, secreting inflammatory cytokines, recruiting conventional T cells and maturing dendritic cells resulting in the priming of adaptive immunity. The MR1-MAIT cell axis has been implicated in immunity against a range of major bacterial pathogens primarily in mucosal tissues. MR1 is also essential for the development and expansion of MAIT cells.
However, despite the key role of MR1 in antibacterial immunity, the specific cell types that express and present MR1 in vivo during steady-state or infection are not known. The MR1 gene is considered ubiquitously transcribed, but direct evidence of protein expression in different cell types is lacking because, unlike other antigen-presenting molecules, MR1 is expressed at very low levels or not at all in the steady-state and this limits the use of traditional detection methods such as flow cytometry. Transcriptomics databases suggest some cell types express more MR1 than others, but a systematic expression map is lacking.
To address this gap in MR1 biology we aimed to identify MR1-expressing cell types in mice by generating a fluorescence expression reporter. A fluorescent gene (tdTomato) was inserted into the locus of MR1, and cells expressing MR1 will produce tdTomato facilitating detection by flow cytometry. Preliminary data suggest that some cell types, including a population of double-positive thymocytes, do in fact express high levels of tdTomato, and this correlates with MR1 expression in wild-type mice determined by qPCR. The expression of tdTomato in other organs is currently being investigated and future experiments will investigate the expression of MR1 in bacterial infection models. This reporter mouse will allow us to create a systematic MR1 expression map in mice and will reveal insights into the mechanism of the MR1 detection of bacteria.