Schematic representation of activating and inhibitory immune receptors.

The prototype activating receptor is composed of a glycoprotein subunit containing an extracellular domain (often with an immunoglobulin-like or lectin-like structure) that is responsible for ligand binding. The ligand-binding receptor lacks intrinsic signaling activity, but pairs with an adapter protein possessing one or more ITAM in the cytoplasmic domain. The immunoreceptor tyrosine-based activation motifs (ITAM)-bearing adaptor protein, such as DAP12, FcεRIγ or CD3ζ are expressed on the cell surface as disulfide-bonded dimers; DAP12 is a homodimer, whereas FcεRIγ or CD3ζ, may form homodimers or heterodimers with each other. After ligand binding, tyrosine phosphorylation of the ITAM causes recruitment and activation of Syk or ZAP70 tyrosine kinases. The receptor and signaling adapter associate via interactions in their transmembranes, typically by a salt bridge formed by oppositely charged amino acids. The prototype inhibitory receptor has a ligand-binding extracellular domain and one or more immunoreceptor tyrosine-based inhibition motifs (ITIM) in the cytoplasmic region of the polypeptide. Binding of ligand causes tyrosine phosphorylation of the ITIM, resulting in recruitment and activation of a tyrosine phosphatase (SHP-1 or SHP-2) or a lipid phosphatase (SHIP-1 or SHIP-2).