Epstein-Barr Virus gp350-Specific Antibody Titers And Antibody-Dependent Cellular Cytotoxic Effector Function In Different Groups Of Patients: A Study Using Cloned gp350-Expressing Transfected Human T Cell Targets

Abstract

An NK cell activity-resistant human lymphoid T cell line (CEM-NKr) expressing the transfected Epstein-Barr virus (EBV) gp350 gene was used in membrane immunofluorescence (MIF) and antibody-dependent cellular cytotoxicity (ADCC) assays to analyze the gp350-specific humoral and ADCC responses in groups of EBV-seropositive persons. Results show that there is no correlation between gp350-specific ADCC-mediating antibody titers and MIF or EBV neutralizing antibody titers. For example, sera from patients in the acute phase of infectious mononucleosis, while positive by MIF assay or EBV neutralization test, were not reactive in the ADCC assay. Results also show that nasopharyngeal carcinoma (NPC) patients on MIF present high IgG titers against gp350 compared with healthy persons. Anti-gp350 IgA antibodies were detected in all groups tested; however, titers were highest in the NPC group.

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

“…In part, these glycoproteins are incorporated in the virion envelope, mediating binding to and fusion with susceptible host cell membranes and thereby form a target for virus-neutralising antibody responses. On the other hand, these glycoproteins are also expressed on the nuclear membrane (gp125/110; Lee 1999) and plasma membrane of virusproducing cells (gp350/220; Thorley-Lawson and Geilinger 1980), thus functioning as target for cytolytic antibody responses capable of killing the target cell either through complement deposition/activation or through action of Fc-receptorbearing killer cells (Khyatti et al 1994;Jilg et al 1994). …”

The Epstein-Barr Virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases

“…Lack of a suitable model for studying anti-gp350 immune responses in these EBV-associated diseases was a major deterrence in the past. However, to make such studies feasible, we developed permanent cell lines expressing gp350 and showed that these cell lines were invaluable tools in studying gp350-specific antibody-dependent cellular cytotoxicity (ADCC) and anti-gp350 antibody titres in EBV-seropositive individuals (Khyatti et al, 1991(Khyatti et al, , 1994. In the present study, using these cell lines, we investigated the gp350-specific ADCC activity and antibody titres in sera of patients with HD, chronic symptomatic EBV infection (CEI), acute infectious monocucleosis (IM) and NPC and compared these with those of healthy EBV-seropositive individuals.…”

Clinical Relevance of Serum Immunoglobulin A Antibodies to Epstein-Barr Virus Envelope Glycoprotein gp350 in Nasopharyngeal Carcinoma Patients

“…These results suggest the existence of differential humoral immune responses to these two viral antigens in NPC patients and underscore the point that determining anti-gp350 IgA antibody titers is of diagnostic value for NPC in individuals who remain negative for anti-VCA IgA. Although anti-gp350 IgA has been detected in the sera of a low proportion of healthy EBV-seropositive individuals, their titers are significantly lower than those found in NPC sera (1,5). In our test system, in which we use gp350expressing T-cell clones in membrane immunofluorescence assays (1) and the cells are examined with a flow cytometer, sera from some healthy EBV-seropositive individuals were found to be positive for anti-gp350 IgA at dilutions of Յ1:10.…”

“…As part of our work with specific immune responses to the EBV major envelope glycoprotein gp350 in different EBVassociated diseases, we compared anti-VCA IgA and gp350specific IgA titers in sera obtained (after written and informed consent was given) from 40 Malaysian NPC patients. The sera were titrated for anti-VCA IgA and anti-gp350 IgA by immunofluorescence (1,4). As shown in Table 1, 70% of these sera were positive for anti-VCA IgA whereas 60% were positive for anti-gp350 IgA.…”