Figure 1.

FcγRs mediate internalization of IgG-ICs. 1. IgG-ICs bind to low-affinity FcγRs at the cell surface of APCs. In the case of activating FcγRs, for instance FcγRIIA, these either contain intracellular ITAM sequences (purple), or are associated with ITAM containing FcRγ (not shown) as described in section The Molecular Machinery Downstream of FcγR and Figure 3. 2. Cross-linking of activating FcγRs leads to ITAM phosphorylation and clathrin-mediated internalization of the FcγR:IgG-IC aggregate with subsequent IgG-IC transport to lysosomes. 3. Inside the lysosomal compartment, both FcγRs and the internalized antigen are proteolytically degraded and eventually loaded onto MHC class II complexes, processes that depend on cathepsin, and HLA-DM activity (not shown). 4. MHC class II peptide complexes are shuttled from the endolysosomal compartment to the cell membrane in order to present antigen-derived peptides (usually 13–25aa in size) to cells of the adaptive immune system. Yellow arrow: In a process termed cross-presentation, non-“self” antigens internalized through FcγR cross-linking can also be shuttled to the cytoplasm, where they are processed similarly to endogenous proteins. The resulting 9–10-aa long peptides will then be incorporated in MHC class I protein complexes.