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Cells expressing the low-affinity Fc\u03b3Rs (Fc\u03b3RII or CD32 and Fc\u03b3RIII or CD16) are activated for these functions when receptors are aggregated following the binding of IgG-opsonized targets. Despite the diversity of the Fc receptor proteins, IgG ligands, and potential responding cell types, the induction of all Fc\u03b3R-mediated responses by opsonized targets requires the presentation of multiple Fc regions in close proximity to each other. We demonstrated that such \u201cnear-neighbor\u201d Fc regions can be detected using defined recombinant soluble (rs) dimeric low-affinity ectodomains (rsFc\u03b3R) that have an absolute binding requirement for the simultaneous engagement of two IgG Fc regions. Like cell surface\u2013expressed Fc\u03b3Rs, the binding of dimeric rsFc\u03b3R ectodomains to Ab immune complexes was affected by Ab subclass, presentation, opsonization density, Fc fucosylation, or mutation. The activation of an NK cell line and primary NK cells by human IgG-opsonized influenza A hemagglutinin correlated with dimeric rsFc\u03b3RIIIa binding activity but not with Ab titer. Furthermore, the dimeric rsFc\u03b3R binding assay sensitively detected greater Fc receptor activity to pandemic H1N1 hemagglutinin after the swine influenza pandemic of 2009 in pooled human polyclonal IgG. Thus these dimeric rsFc\u03b3R ectodomains are validated, defined probes that should prove valuable in measuring the immune-activating capacity of IgG Abs elicited by infection or vaccination or experimentally derived IgG and its variants.<\/jats:p>","DOI":"10.4049\/jimmunol.1502551","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T01:31:02Z","timestamp":1467855062000},"page":"1507-1516","source":"Crossref","is-referenced-by-count":112,"title":["Dimeric Fc\u03b3R Ectodomains as Probes of the Fc Receptor Function of Anti-Influenza Virus IgG"],"prefix":"10.1093","volume":"197","author":[{"given":"Bruce D","family":"Wines","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]},{"name":"Department of Immunology, Monash University Central Clinical School , Melbourne, Victoria 3004,","place":["Australia"]},{"name":"Department of Pathology, The University of Melbourne , Melbourne, Victoria 3052,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary A","family":"Vanderven","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria 3052,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E","family":"Esparon","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne B","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria 3052,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Parkville, Victoria 3052,","place":["Australia"]},{"name":"Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne , Parkville, Victoria 3052,","place":["Australia"]},{"name":"Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Monash University Central Clinical School , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Mark","family":"Hogarth","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]},{"name":"Department of Immunology, Monash University Central Clinical School , Melbourne, Victoria 3004,","place":["Australia"]},{"name":"Department of Pathology, The University of Melbourne , Melbourne, Victoria 3052,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,15]]},"reference":[{"key":"2025030617473154800_r1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2174\/1570162X113116660059","article-title":"Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity [ADCC] responses","volume":"11","author":"Pollara","year":"2013","journal-title":"Curr. 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