Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG

Abstract

TYPE III receptors for IgG (FcγRII; ref. 1), high-affinity IgE receptors (FcɛRI; ref. 2), as well as the T- and B-cell antigen receptors^3,4, consist of multiple components with specialized ligand-binding and signal transduction functions^5–10. FcγRII α (ligand-binding) and γ (signal-transducing) subunits are expressed in macrophages¹, a cell type involved in the uptake of antigen, its processing and the presentation of the resulting peptides to major histocompatibility complex class II-restricted T lymphocytes^11,12. Here we show that murine FcγRIII, transfected into FcγR-negative antigen-presenting B-lymphoma cells, mediate rapid ligand internalization and strongly increase the efficiency of antigen presentation when antigen is complexed to IgG. Efficient internalization and antigen presentation via FcγRIII did not require the cytoplasmic domain of the ligand-binding α-chain, but did require the γ-subunit. Using chimaeric molecules, we show that γ-chain contains a signal for receptor internalization and that the mutation of either of the two ryrosine residues present in its cytoplasmic domain prevents efficient internalization and antigen presentation of immune complexes. Thus, associated chains and their tyrosine-containing motif are not exclusively involved in cell activation, but also determine multimeric receptor internalization.