The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages.
Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc gamma R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc gamma R on feline macrophage.
Department of Veterinary Infectious Diseases, School of Veterinary Medicine and Animal Sciences, Kitasato University, Anomori, Japan.
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T
Hohdatsu
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Tokunaga
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H
Koyama
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D002415:Cats; D016765:Coronavirus, Feline / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000821:virology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000821:virology; D017452:Receptors, IgG / Q000378:metabolism; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins