The human cytomegalovirus Fc receptor gp68 binds the Fc CH2-CH3 interface of immunoglobulin G

Recognition of immunoglobulin G (IgG) by surface receptors for the Fc domain of immunoglobulin G (Fc gamma), Fc gamma Rs, can trigger both Immoral and cellular immune responses. Two human cytomegalovirus (HCMV)encoded type I transmembrane receptors with Fc gamma-binding properties (vFc gamma Rs), gp34 and gp68, have been identified on the surface of HCW-infected cells and are assumed to confer protection against IgG-mediated immunity. Here we show that Fc gamma recognition by both vFc gamma Rs occurs independently of N-linked glycosylation of Fc gamma, in contrast with the properties of host Fc gamma Rs. To gain further insight into the interaction with Fc gamma, truncation mutants of the vFc gamma R gp68 ectodomain were probed for Fc gamma binding, resulting in localization of the Fc gamma binding site on gp68 to residues 71 to 289, a region including an immunoglobulin-like domain. Gel filtration and biosensor binding experiments revealed that, unlike host Fc gamma Rs but similar to the herpes simplex virus type I (HSV-1) Fc receptor gE-gI, gp68 binds to the C(H)2-C(H)3 interdomain interface of the Fc gamma dimer with a nanomolar affinity and a 2:1 stoichiometry. Unlike gE-gI, which binds Fc gamma at the slightly basic pH of the. extracellular milieu but not at the acidic pH of endosomes, the gp68/Fc gamma complex is stable at pH values from 5.6 to pH 8.1. These data indicate that the mechanistic details of Fc binding by HCMV gp68 differ from those of host Fc gamma Rs and from that of HSV-1 gE-gI, suggesting distinct functional and recognition properties.