The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the from proteasomal breakdown and, as measured in cytotoxicity assays, major histocompatibility complex (MHC) class I–restricted presentation CD8+ T cells. This led concept of EBNA1 an immunologically silent protein although unique being expressed all EBV malignancies, could not be exploited CD8 target. Here, using cell clones native epitopes upstream and downstream...

ABSTRACT There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4 + T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require T-cell recognition latently infected through epitopes derived from endogenously expressed viral proteins and presented on target cell surface association with HLA class II molecules. It therefore important know how often these conditions are met. Here we provide epitope...

Whereas exogenously acquired proteins are the major source of antigens feeding MHC class II pathway in antigen-presenting cells, some endogenously expressed also access that but rules governing such poorly understood. Here we address this using Epstein–Barr virus (EBV)-coded nuclear antigen EBNA1, a protein naturally EBV-infected B lymphoblastoid cell lines (LCLs) and multiple CD4 + T epitopes. Using clones against three indicator epitopes, find two epitopes weakly displayed on LCL surface...

Abstract Interactions between MHC class II (MHC II)‐positive APCs and CD4 + T cells are central to adaptive immune responses. Using an Epstein–Barr virus (EBV)‐transformed B lymphoblastoid cell line (LCL) as II‐positive T‐cell clones specific for two endogenously expressed EBV antigens, we found that shRNA knockdown of the tetraspanin protein CD63 in LCL consistently led increased recognition. This effect was not due enhanced antigen processing nor changes expression since did influence...

Abstract Mouse models suggest that the processing of exogenous Ag by dendritic cells can be important for priming CD8+ CTL response. To study situation in humans, we have exploited response to EBV infection. In this context expresses eight latent proteins, which EBV-encoded nuclear (EBNA) 3A, 3B, and 3C appear immunodominant responses, whereas another Ag, EBNA1, is completely protected from endogenous presentation via MHC class I pathway, thought induce responses rarely, if ever. Here, using...

ABSTRACT Virus-associated malignancies are potential targets for immunotherapeutic vaccines aiming to stimulate T-cell responses against viral antigens expressed in tumor cells. Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high-incidence southern China, expresses limited set of EBV proteins, including the nuclear antigen EBNA1, an abundant source HLA class II-restricted CD4 + epitopes, and latent membrane protein LMP2, subdominant CD8 epitopes presented by I alleles common...

Evasion of immune T cell responses is crucial for viruses to establish persistence in the infected host. Immune evasion mechanisms Epstein-Barr virus (EBV) context MHC-I antigen presentation have been well studied. In contrast, viral interference with MHC-II less understood, not only EBV but also other persistent viruses. Here we show that encoded BZLF1 can interfere recognition by CD4+ effector cells. This impaired occurred absence a reduction expression surface MHC-II, correlated marked...

The Epstein-Barr virus (EBV) is one of the predominant tumor viruses in humans, but so far no therapeutic or prophylactic vaccination against this transforming pathogen available. We demonstrated that heterologous prime-boost with nuclear antigen 1 EBV (EBNA1), either targeted to DEC205 receptor on DCs expressed from a recombinant modified vaccinia Ankara (MVA) vector, improved priming antigen-specific CD4+ T cell help. This help supported expansion and maintenance EBNA1-specific CD8+ cells...

Abstract The CD4+ T cell response to EBV may have an important role in controlling virus-driven B lymphoproliferation because clones a subset of nuclear Ag (EBNA) epitopes can directly recognize virus-transformed lymphoblastoid lines (LCLs) vitro and inhibit their growth. In this study, we used panel EBNA1, 2, 3A, 3C-specific study the route whereby endogenously expressed EBNAs access HLA class II-presentation pathway. Two sets results spoke against direct intracellular access. First, none...

Abstract The EBV-latent membrane proteins (LMPs) 1 and 2 are among only three viral expressed in EBV-associated Hodgkin’s lymphoma nasopharyngeal carcinoma. Since these tumors HLA class I II-positive, the LMPs could serve as both CD8+ CD4+ T cell targets. In contrast to CD8 responses, very little is known about CD4 responses LMPs. this study, we describe clones defining four LMP1- LMP2-derived peptide epitopes their restricting alleles. All produced Th1-like cytokines response most killed...

CD4+ T cells recognize a broad range of peptide epitopes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which contribute to immune memory and limit COVID-19 disease. We demonstrate that the immunogenicity SARS-CoV-2 peptides, in context model allotype HLA-DR1, does not correlate with their binding affinity HLA heterodimer. Analyzing six epitopes, some very low affinity, we solve X-ray crystallographic structures each bound HLA-DR1. Further structural definitions reveal precise...

Epstein-Barr virus (EBV) latent membrane protein (LMP)2 is a multiple spanning molecule which lacks ectodomains projecting into the lumen of endoplasmic reticulum (ER). Human CD8+ cytotoxic T lymphocytes (CTL)s recognize number epitopes within LMP2. Assays with epitope-specific CTLs in two different cell backgrounds lacking transporter associated antigen processing (TAP) consistently show that some, but not all, LMP2 are presented TAP-independent manner. However, unlike published examples...

Background Epstein-Barr virus (EBV) is a likely prerequisite for multiple sclerosis (MS) but the underlying mechanisms are unknown. We investigated antibody and T cell responses to EBV in persons with MS (pwMS), healthy EBV-seropositive controls (HC) post-infectious mononucleosis (POST-IM) individuals up 6 months after disease resolution. The ability of EBV-specific target antigens from central nervous system (CNS) was also investigated. Methods Untreated relapsing-remitting MS, POST-IM HC...

We have identified an HLA-A2-restricted CD8(+) T-cell epitope, FLYALALLL, in the Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2), important target antigen context of EBV-associated malignancies. This epitope is TAP independent, like other hydrophobic LMP2-derived epitopes, but uniquely dependent upon immunoproteasome for its generation.

Abstract The COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. scientific community responded by developing several efficacious vaccines which were expedited need for vaccines. emergence of SARS‐CoV‐2 breakthrough infections highlights additional vaccine modalities provide stronger, long‐lived protective immunity. Here we report design preclinical testing small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines...

ABSTRACT Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies immune evasion persistence have been proposed based on studies of EBV infection humans, but it has difficult to test their actual contribution experimentally. Interest focused nuclear antigen 1 (EBNA1) because its essential role maintenance replication episomal viral genome...

Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (Ad) cause significant morbidity mortality in immunocompromised patients undergoing allogeneic stem cell transplantation. We have established a procedure to generate polyclonal cytotoxic T lymphocyte (CTL) populations with specificity against Ad CMV or EBV. Healthy donor-derived dendritic cells (DCs) were transduced recombinant encoding either pp65 EBV EBNA3C used stimulate autologous cells. Stimulated lymphocytes displayed...

T-cell memory to Epstein-Barr virus (EBV) was first demonstrated through regression of EBV-induced B-cell transformation lymphoblastoid cell lines (LCLs) in virus-infected peripheral blood mononuclear (PBMC) cultures. Here, using donors with virus-specific well-defined CD4 and CD8 epitopes, we reexamine recent reports that the effector cells mediating are EBV latent antigen-specific CD4+ not, as previously assumed, CD8+ T cells. In regressing cultures, find reversal CD23+ proliferation...

Abstract Alloreactive T cells play a key role in mediating graft-vs-host disease and allograft rejection, recent data suggest that most cell alloreactivity resides within the CD4 subset. Particularly, responses to herpesvirus can shape alloreactive repertoire influence transplantation outcomes. In this study, we describe six distinct EBV-specific CD4+ clones cross-reacted with EBV-transformed lymphoblastoid lines (LCLs), dendritic cells, endothelial expressing MHC class II alleles commonly...

Epstein Barr Virus (EBV) infects more than 95% of the population whereupon it establishes a latent infection B-cells that persists for life under immune control. Primary EBV can cause infectious mononucleosis (IM) and long-term viral carriage is associated with several malignancies certain autoimmune diseases. Current efforts developing prophylactic vaccination have focussed on neutralising antibodies. An alternative strategy, could enhance efficacy such vaccines or be used alone, to...

Shear forces are proposed to explain the failure of antiglobulin and 'neutral' (no antiglobulin) microcolumn tests at 37 degrees C detect weak ABO incompatibilities other antibodies, clearly detectable by spin-tube methods. These shear can be minimized in a test using biphasic centrifugation phase. Although this is not suitable for routine use, it may use as an investigational method reference laboratories. This little clinical significance antibodies dubiously active C.