TYROSINE-CONTAINING MOTIF THAT TRANSDUCES CELL ACTIVATION SIGNALS ALSO DETERMINES INTERNALIZATION AND ANTIGEN PRESENTATION VIA TYPE-III RECEPTORS FOR IGG

TYPE III receptors for IgG (Fc-gamma-RII; ref. 1), high-affinity IgE receptors (Fc-epsilon-RI; ref. 2), as well as the T- and B-cell antigen receptors3,4, consist of multiple components with specialized ligand-binding and signal transduction functions5-10. Fc-gamma-RII-alpha (ligand-binding) and gamma (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 lymphocytes11,12. Here we show that murine Fc-gamma-RIII, transfected into Fc-gamma-R-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 Fc-gamma-RIII did not require the cytoplasmic domain of the ligand-binding alpha-chain, but did require the gamma-subunit. Using chimaeric molecules, we show that gamma-chain contains a signal for receptor internalization and that the mutation of either of the two tyrosine 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.