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. Author manuscript; available in PMC: 2017 Jul 1.
Published in final edited form as: Immunol Rev. 2016 Jul;272(1):65–79. doi: 10.1111/imr.12428

Figure 2. Toll-like receptor signals divert the traffic of MHC-I molecules from the ERC to phagosomes.

Figure 2

Three types of internalization events are depicted in this schematic. Clathrin-independent endocytosis (CIE) of MHC-I molecules, clathrin-mediated endocytosis (CME) of transferrin and phagocytosis of bacteria. Endosomes carrying the CIE cargo MHC-I and the CME cargo transferrin receptor converge into the sorting endosome, but maintain segregation in distinct subdomains. Although both MHC-I and transferrin receptor can undergo ‘fast recycling’, transferrin receptor is shown here recycling back to the plasma membrane through ‘fast recycling’. MHC-I molecules are shown entering the ERC through ‘slow recycling’. TLR signaling dependent on MyD88 and IKK2 leads to the phosphorylation of the synaptosomal associated protein SNAP23, which serves to stabilize trans-SNARE complexes between phagosomal Q-SNAREs (one candidate is Syntaxin 4) and ERC R-SNARE (VAMP8/cellulbrevin is a candidate). The resultant TLR-induced stable SNARE pins drive fusion between the MHC-I rich ERC and the microbial antigen containing phagosome. The fusion event delivers MHC-I molecules from the ERC to the phagosome. Microbial peptide-loaded MHC-I then travel to the plasma membrane to be displayed for recognition by microbe-specific CD8 T cells.