Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ

Upon receptor activation, the myeloid C-type lectin receptor Mincle signals via the Syk-CARD9-Bcl10-MALT1 pathway. It does so by recruiting the ITAM-bearing Fc epsilon RI-. The related receptor macrophage C-type Lectin (MCL) has also been shown to be associated with Syk and to be dependent upon this signaling axis. We have previously shown that MCL co-precipitates with Fc epsilon RI-, but were unable to show a direct association, suggesting that MCL associates with Fc epsilon RI- via another molecule. Here, we have used rat primary cells and cell lines to investigate this missing link. A combination of flow cytometric and biochemical analysis showed that Mincle and MCL form heteromers on the cell surface. Furthermore, association with MCL and Fc epsilon RI- increased Mincle expression and enhanced phagocytosis of Ab-coated beads. The results presented in this paper suggest that the Mincle/MCL/Fc epsilon RI- complex is the functionally optimal form for these C-type lectin receptors on the surface of myeloid cells.