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A Model System to Investigate Antibody Bipolar Bridging Mediated by gE‐gI, a Herpes Virus Fc Receptor
Author(s) -
Ndjamen Blaise,
Farley Alexander,
Bjorkman Pamela J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.605.8
Subject(s) - antigen , antibody , virology , immune system , chemistry , immunoglobulin g , virus , immune complex , monoclonal antibody , microbiology and biotechnology , biology , immunology
The Herpes Simplex Virus 1 (HSV‐1) expresses two membrane glycoproteins (gE and gI) that bind the Fc region of host immunoglobulin G (IgG), which allows HSV‐infected cells to escape recognition by Fc‐dependent immune cells. HSV‐1 gE‐gI can further undermine the immune system by participating in antibody bipolar bridging (ABB), a process by which the antigen‐binding fragments of the IgG bind a viral antigen while the Fc binds to gE‐gI. The fate of the gE‐gI/IgG/viral antigen ABB complex is still unknown. In this study, we engineered an in vitro ABB system to determine whether the gE‐gI/IgG/viral antigen complex is internalized and targeted for degradation in host cells. This system involves HeLa cells transiently expressing HSV‐1 gE‐gI and HSV‐1 gD; and two forms of the monoclonal anti‐gD antibody: one in which the Fabs were fused to a human IgG1 Fc (hIgG), which can bind to gE‐gI via its Fc and to gD via its Fabs, and one in which the Fabs were fused to a mouse IgG2a Fc (mIgG), which can bind to gD but not to gE‐gI. A hIgG against an irrelevant HIV‐1 antigen was used as a control. Time‐lapse confocal imaging showed that gE‐gI internalized hIgG/gD but not mIgG/gD; internalized IgG and gD were targeted into degradative compartments. These results suggest that gE‐gI plays an active role in clearing the infected cell surface of both host IgG and viral antigens, providing HSV‐1 with a mechanism to evade the immune responses.