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The Human Cytomegalovirus Fc Receptor gp68 Binds the Fc CH2-CH3 Interface of Immunoglobulin G

Sprague, Elizabeth R. and Reinhard, Henrike and Cheung, Evelyn J. and Farley, Alexander H. and Deis Trujillo, Robin and Hengel, Helmut and Bjorkman, Pamela J. (2008) The Human Cytomegalovirus Fc Receptor gp68 Binds the Fc CH2-CH3 Interface of Immunoglobulin G. Journal of Virology, 82 (7). pp. 3490-3499. ISSN 0022-538X. PMCID PMC2268481. doi:10.1128/JVI.01476-07.

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Recognition of immunoglobulin G (IgG) by surface receptors for the Fc domain of immunoglobulin G (Fc{gamma}), Fc{gamma}Rs, can trigger both humoral 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 HCMV-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 1 (HSV-1) Fc receptor gE-gI, gp68 binds to the CH2-CH3 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.

Item Type:Article
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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2008, American Society for Microbiology. Received 5 July 2007/ Accepted 15 January 2008. Published ahead of print on 23 January 2008. We thank Peter Snow and Inder Nangiana for insect cell expression of gp68 proteins, Brian Seed for the CD64 and CD32 cDNAs, Manuela Fiedler and Philipp Lacher for constructing rVVs, and Eugenia Corrales-Aguilar for critical reading of the manuscript. This work was supported by a Leukemia and Lymphoma Society Postdoctoral Fellowship (E.R.S.), a Max Planck Research Award (P.J.B.), the National Institutes of Health (2 R37 AI041239-06A1 to P.J.B.), DFG grant He 2526/6-2, and EU grant FP6-037517.
Funding AgencyGrant Number
Leukemia and Lymphoma SocietyUNSPECIFIED
Max Planck SocietyUNSPECIFIED
NIH2 R37 AI041239-06A1
European Research Council (ERC)He 2526/6-2
European UnionFP6-037517
Issue or Number:7
PubMed Central ID:PMC2268481
Record Number:CaltechAUTHORS:SPRAjvir08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9761
Deposited By: Archive Administrator
Deposited On:14 Mar 2008
Last Modified:01 Jun 2023 23:32

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