Figure 5

Model for MR1 trafficking. (A) MR1 is synthesized in the ER. Some MR1 is able to leave the ER, perhaps with an unidentified endogenous ligand. MR1 captures Mtb antigens via 3 potential pathways: First, MR1 is recycled from the plasma membrane into an endosome that samples the Mtb phagosome. Second, MR1 interacts with Mtb after MR1 exits the trans-Golgi network. Third, MR1 in the ER captures Mtb antigens. Knockdown of the endosomal trafficking proteins VAMP2 and Syntaxin 16 affect Mtb-dependent antigen presentation. (B) 6-FP binds MR1 in the ER. 6-FP bound MR1 recycles into a compartment that is suitable for loading of exogenously delivered antigens. After binding exogenous antigens, MR1 traffics back to the cell surface. Syntaxin 4 knockdown blocks the ability of MR1 bound to exogenous antigen to activate T cells. VAMP2 and STX16 also affect presentation of exogenously delivered antigens.