Macrophages are specialised at MR1 antigen presentation to MAIT cells [ATAC-seq]

Mucosal associated invariant T (MAIT) cells are lymphocytes that mediate tissue homeostasis and antimicrobial immunity. MAIT cells recognize microbial vitamin B-derived antigens (VitBAg) presented by MHC class I-related protein 1 (MR1). The cells that express MR1 and present VitBAg to MAIT cells remain unknown. We found that MR1 expression varies across tissues and cell types. Expression is regulated transcriptionally and induced by the tissue environment and microbiota. Depletion of MR1 in macrophages, dendritic cells and monocytes changed the composition of the microbiota and impaired MAIT cell responses against bacteria infection. Macrophages expressed the highest levels of MR1 and were the most efficient at capturing and presenting VitBAg to MAIT cells. We conclude that macrophages are key players in MR1 antigen presentation and MAIT cell immunity. Overall design: Different cell types were isolated from C57BL/6J mice that were maintained in either Specific Pathogen Free or Germ Free conditions. These included B cells, alveolar macrophages and peritoneal macrophages that have a range of MR1 expression. Then ATAC-seq was performed to understand if the accessibility of the Mr1 gene correlated with its expression.