Figure 2. FcγR ligation and the fate of antigens.

Antigens in ICs entering APCs via different FcγRs show distinct trafficking patterns. In general, FcγRIIb‐mediated uptake traps the cargo in non‐degrading vesicles for prolonged extracellular release of antigens in their native forms. This feature is important for B‐cell activation. Activating FcγR‐mediated entry may direct the cargo into two routes. One is through the shallow early endosomes whereby the antigens are recycled to the cell surface in complex with MHC class I molecule for cross‐presentation. The other route leads the antigens to the MHC class II compartment (a branch of late endo/lysosomal compartment) and epitope peptides generated in this harsher environment are loaded onto MHC class II molecules for conventional CD4 T‐cell activation. The ITAM motif present in FcγRs (intrinsic or in the common γ‐chain) recruits Syk and activates signal transducers of PLC, PKC, and PI3K leading to APC activation. Syk signaling may assist the class II peptide exchange regulated by class II‐like DM/DO molecules in the MHC class II compartment.