Binding of the endogenously expressed Epstein-Barr virus (EBV) envelope glycoprotein gp350 with the viral receptor masks the major EBV-neutralizing epitope and affects gp350-specific ADCC.
The major neutralizing epitope (MNE) for the Epstein-Barr virus (EBV) is present on its envelope glycoprotein gp350/220 (hereafter referred to as gp350) in close proximity to the virus-receptor (CR2) binding site and is recognized by the neutralizing murine monoclonal antibody (mAb) 72A1. We studied the reactivities of 72A1 and another anti-gp350 mAb 2L10 (which does not neutralize EBV) with gp350 expressed on three different lymphoid cell lines (Raji, CEM.NKr and BJA-B). Our results indicate that gp350 expressed on the surface of CR2-positive cells interacts with the viral receptor and that this interaction masks the major EBV-neutralizing epitope. The interaction was reversible and the masked epitope was revealed on incubation with an excess of anti-CR2 mAb OKB7. Gp350-expressing CEM-NKr cells with intact MNE exhibited significantly higher (P < or = 0.05) lysis in gp350-specific antibody-dependent cellular cytotoxic assays compared with its Raji counterpart. The present results may have important implications for the use of soluble viral receptors as therapeutic agents in acute and chronic EBV and other viral infections (e.g., HIV-1).
Khyatti
M
M
Laboratory of Immunovirology, University of Montreal, Quebec, Canada.
Ahmad
A
A
Blagdon
M
M
Frade
R
R
Menezes
J
J
D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D009500:Neutralization Tests; D011863:Radioimmunoassay; D017464:Receptors, Complement 3d / Q000276:immunology* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; C034059:GP 300-350, Epstein-Barr virus; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins