Epstein-Barr virus (EBV) glycoprotein gp350 expressed on transfected cells resistant to natural killer cell activity serves as a target antigen for EBV-specific antibody-dependent cellular cytotoxicity

Khyatti, Meriem; Patel, Pravin; Stefănescu, I; Menezes, José

doi:10.1128/jvi.65.2.996-1001.1991

Cited by 48 publications

(16 citation statements)

References 25 publications

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“…Our data support that Ab-dependent activation enhances the NK cell response to EBV-infected B cells and may have an important role in the control of this herpesvirus infection following the development of the T and B cell adaptive response. In agreement with previous reports (26), the presence of the gp350 envelope Ag on the surface of infected cells was associated with the ability of serum Abs to trigger NK cell degranulation and cytokine production. Ab-dependent activation was preferentially directed against AKBM cells in the lytic cycle, as previously reported for the direct NK cell response (9).…”

Section: Discussionsupporting

confidence: 92%

“…In addition to their direct interaction with target cells, which involves an array of inhibitory, activating, and costimulatory receptors, NK cells are the main effectors of Ab-dependent effector mechanisms triggered by FcgR-IIIA (CD16). Early studies identified ADCC as a mechanism of immune response to EBV-infected cells (24)(25)(26), and this issue has been re-explored in detail in this study.…”

Section: Discussionmentioning

confidence: 85%

“…CD16 was the first characterized NKR, and the importance of ADCC in the control of different viral infections is being increasingly appreciated (20)(21)(22)(23), yet few studies have addressed its role in the defense against EBV. Some pioneer reports described NK cell-mediated ADCC against EBV-infected cells, identifying as a major target Ag the late lytic cycle gp350/220 molecule, which is involved in the pathogen interaction with CD21 (CR2) expressed on B cells (24)(25)(26). This initial step in the infection process was reported to be inhibited by CD21 binding of gp350 + exosomes that are released by EBV-infected cells (27).…”

Section: Antibody-dependent Nk Cell Activation Differentially Targetsmentioning

confidence: 99%

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Antibody-Dependent NK Cell Activation Differentially Targets EBV-Infected Cells in Lytic Cycle and Bystander B Lymphocytes Bound to Viral Antigen–Containing Particles

López-Montañés

Alari-Pahissa

Sintes

et al. 2017

The Journal of Immunology

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NK cells have been reported to respond against EBV-infected B cells in the lytic cycle and to control the viral infection involving IFN-γ secretion. Early reports proposed a role for NK cell Ab-dependent cellular cytotoxicity (ADCC) triggered via FcγR-IIIA (CD16) in the response to EBV. In the current study, we revisited this issue, showing that serum from EBV individuals triggered vigorous NK cell degranulation and cytokine production (i.e., TNF-α and IFN-γ) against EBV-infected cells, enhancing NK cell activation. The effect was preferentially directed against cells in the lytic phase and was associated with surface expression of the gp350/220 envelope Ag. In contrast, binding of gp350 particles, released by EBV-infected cells, to B cell lines or autologous primary B lymphocytes also promoted specific Ab-dependent NK cell degranulation and TNF-α production but induced minimal IFN-γ secretion. In that case, target cell damage appeared marginal compared with the effect of a control anti-CD20 Ab (rituximab) at concentrations that triggered similar NK cell activation, indicating that cell-associated gp350 particles may divert the cytolytic machinery, impairing its direct action on the plasma membrane. These observations support that Ab-dependent NK cell activation plays an important role in the control of EBV, enhancing NK cell effector functions against infected B cells in the lytic cycle. In contrast, the data reveal that gp350 particles bound to bystander B cells trigger Ab-dependent NK cell degranulation and TNF-α but not cytotoxicity or IFN-γ production, potentially favoring the progression of viral infection.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Section: Antibody-dependent Nk Cell Activation Differentially Targetsmentioning

confidence: 99%

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Antibody-Dependent NK Cell Activation Differentially Targets EBV-Infected Cells in Lytic Cycle and Bystander B Lymphocytes Bound to Viral Antigen–Containing Particles

López-Montañés

Alari-Pahissa

Sintes

et al. 2017

The Journal of Immunology

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“…Several components of the immune system contribute to the highly efficient control of virus replication and proliferation of immortalized EBV-infected cells in healthy individuals. NK cells as well as antibody-dependent cellular cytotoxicity mechanisms directed against the viral glycoprotein gp350/220 seem to play a role (24,43); neutralizing antibodies prevent endogenous reinfection through virus particles released by epithelial cells or lymphocytes. The best-characterized and probably the most important components of these mechanisms, however, are HLA-restricted specific cytotoxic T lymphocytes (CTL) directed against viral gene products of the latent state.…”

mentioning

confidence: 99%

Immediate-Early Transactivator Rta of Epstein-Barr Virus (EBV) Shows Multiple Epitopes Recognized by EBV-Specific Cytotoxic T Lymphocytes

et al. 1998

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We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV) for its role as a target for specific cytotoxic T lymphocytes (CTL). Panels of overlapping peptides covering the entire amino acid sequence of Rta were synthesized and used to induce and analyze specific CTL responses in EBV-positive donors. Using peptide-pulsed target cells, we found nine different CTL epitopes that are distributed over the entire protein sequence. One epitope restricted by HLA-A24 could be mapped to the decameric sequence DYCNVLNKEF between amino acid positions 28 and 37 of the Rta protein. A second epitope could be assigned to the same region of Rta (residues 25 to 39) and was shown to be restricted by HLA-B18. Another, minimal epitope could be mapped to the nonameric sequence ATIGTAMYK between amino acid positions 134 and 142; this peptide was restricted by HLA-A11. Another four epitopes were proven to be restricted by HLA-A2, -A3, -B61, and -Cw4 and were located between Rta residues 225 and 239, 145 and 159, 529 and 543, and 393 and 407, respectively. For two other epitopes, only the location within the Rta protein is known so far (residues 121 to 135 and 441 to 455); their exact HLA restriction patterns have not yet been identified. Using target cells infected with recombinant vaccinia virus containing the gene for Rta, we showed that six of eight Rta-specific CTL lines recognized the corresponding peptides also after endogenous processing. These data suggest that Rta comprises an important target for EBV-specific cellular cytotoxicity. Together with recent findings of other immediate-early and early proteins also acting as CTL targets, they reveal the role of proteins of the lytic cycle in the immune recognition of EBV-infected cells.

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“…Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which causes infectious mononucleosis (IM) and is strongly associated with a number of malignancies, including endemic Burkitt's lymphoma (BL), undifferentiated nasopharyngeal carcinoma (NPC), and other lymphoproliferative diseases (25). Antibodies specific to gp340, the major EBV envelope glycoprotein and receptor ligand (32,41), are functionally active in a number of in vitro assays which include virus neutralization, complement fixation, and antibody-dependent cellular cytotoxicity (3,10,22,(34)(35)(36)42). Such antibodies would appear to provide a large proportion of EBV-specific serum humoral immunity in asymptomatic EBV-seropositive individuals and may therefore have an important role to play in limiting virus spread in vivo.…”

mentioning

confidence: 99%

Mapping of B-cell epitopes on the polypeptide chain of the Epstein-Barr virus major envelope glycoprotein and candidate vaccine molecule gp340

Pither

Zhang

Shiels

et al. 1992

J Virol

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The Epstein-Barr virus (EBV) major envelope glycoprotein gp340 is the subject of current efforts to develop an EBV subunit vaccine. The importance of gp340-specific humoral immunity has been highlighted by studies of natural infection in humans and gp340 immunization of experimental animals. The former studies have demonstrated the presence of gp340-specific serum antibodies which mediate EBV neutralization, complement fixation, and antibody-dependent cellular cytotoxicity. The latter studies have often shown a correlation between the induction of gp340-specific EBV-neutralizing antibodies and protection from virus challenge. We have used a series of bacterial 0-galactosidase-gp340 fusion proteins and overlapping synthetic peptides from the gp340 open reading frame to map the positions of B-cell epitopes within the gp340 primary amino acid sequence. The data reported here indicate the presence of B-cell epitopes within the carboxy-terminal third of the gp340 polypeptide chain. These epitopes could not be detected with a peptide enzyme-linked immunosorbent assay, thereby suggesting that they are discontinuous. Affinity purification of antibodies with a gp340 fusion protein from the carboxy terminus of the gp340 polypeptide chain has been used to show that these antibodies are not EBV neutralizing in vitro. The consequences of these findings for future EBV vaccine development are considered.

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Epstein-Barr virus (EBV) glycoprotein gp350 expressed on transfected cells resistant to natural killer cell activity serves as a target antigen for EBV-specific antibody-dependent cellular cytotoxicity

Cited by 48 publications

References 25 publications

Antibody-Dependent NK Cell Activation Differentially Targets EBV-Infected Cells in Lytic Cycle and Bystander B Lymphocytes Bound to Viral Antigen–Containing Particles

Antibody-Dependent NK Cell Activation Differentially Targets EBV-Infected Cells in Lytic Cycle and Bystander B Lymphocytes Bound to Viral Antigen–Containing Particles

Immediate-Early Transactivator Rta of Epstein-Barr Virus (EBV) Shows Multiple Epitopes Recognized by EBV-Specific Cytotoxic T Lymphocytes

Mapping of B-cell epitopes on the polypeptide chain of the Epstein-Barr virus major envelope glycoprotein and candidate vaccine molecule gp340

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