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J. Virol. doi:10.1128/JVI.01476-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Human Cytomegalovirus Fc Receptor gp68 Binds the Fc C_H2-C_H3 Interface of IgG

Division of Biology, and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA; Institut für Virologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany

^* To whom correspondence should be addressed. Email: bjorkman{at}caltech.edu.

	Abstract

Recognition of IgG by surface receptors for the Fc domain of immunoglobulin G (Fc), FcRs, can trigger both humoral and cellular immune responses. Two human cytomegalovirus (HCMV)-encoded type I transmembrane receptors with Fc-binding properties (vFcRs), gp34 and gp68, have been identified on the surface of HCMV-infected cells, and are assumed to confer protection against IgG-mediated immunity. Here we show that Fc recognition by both vFcRs occurs independent of N-linked glycosylation of Fc, contrasting with the properties of host FcRs. To gain further insight into the interaction with Fc, truncations of the vFcR gp68 ectodomain were probed for Fc binding, resulting in localization of the Fc binding site on gp68 to residues 71 – 289, a region including an immunoglobulin-like domain. Gel filtration and biosensor binding experiments revealed that, unlike host FcRs but similar to the Herpes simplex virus 1 (HSV-1) Fc receptor gE-gI, gp68 binds to the C_H2-C_H3 interdomain interface of the Fc dimer with a nanomolar affinity and a 2:1 stoichiometry. Unlike gE-gI, which binds Fc at the slightly basic pH of the extracellular milieu but not at the acidic pH of endosomes, the gp68/Fc 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 host FcRs and from HSV-1 gE-gI, suggesting distinct functional and recognition properties.