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 si te and is recognized by the neutralizing murine monoclonal antibody (m Ab) 72A1. We studied the reactivities of 72A1 and another anti-gp350 m Ab 2L10 (which does not neutralize EBV) with gp350 expressed on three different lymphoid cell Lines (Raji, CEM.NKr and BJA-B). Our results i ndicate that gp350 expressed on the surface of CR2-positive cells inte racts with the viral receptor and that this interaction masks the majo r EBV-neutralizing epitope. The interaction was reversible and the mas ked epitope was revealed on incubation with an excess of anti-CR2 mAb OKB7. Gp350-expressing CEM-NKr cells with intact MNE exhibited signifi cantly higher (P less than or equal to 0.05) lysis in gp350-specific a ntibody-dependent cellular cytotoxic assays compared with its Raji cou nterpart. The present results may have important implications for the use of soluble viral receptors as therapeutic agents in acute and chro nic EBV and other viral infections (e.g., HIV-1).