Epstein-Barr virus antigens presented on Major Histocompatibility Complex (EBV-MHC) (EBV-MHC)

Epstein-Barr virus (EBV) antigens presented on the Major Histocompatibility Complex (MHC) are a specialized class of tumor-specific targets for immunotherapy (Young et al., 2016, Nature Reviews Cancer). EBV is a gammaherpesvirus associated with several malignancies, including nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder (PTLD). In these cancers, the virus expresses latent proteins such as Latent Membrane Proteins (LMP1, LMP2) and Epstein-Barr Nuclear Antigen 1 (EBNA1), which are processed into short peptides and displayed on the cell surface by MHC molecules (Bollard & Heslop, 2016, Blood). This presentation allows the immune system to identify and eliminate infected cells, making these complexes ideal targets for T-cell-based therapies. Therapeutic approaches targeting EBV-MHC complexes primarily involve adoptive T-cell transfer, including EBV-specific cytotoxic T-lymphocytes (CTLs) and engineered T-cell receptor (TCR-T) therapies. Tabelecleucel is a notable allogeneic T-cell therapy that has received regulatory approval in certain regions for treating EBV-positive PTLD by recognizing these viral peptides on the MHC of malignant cells (Prockop et al., 2020, JCI). Because these viral antigens are not present in healthy human tissue, they offer high therapeutic specificity and a lower risk of off-target effects compared to traditional chemotherapy. However, challenges such as MHC downregulation by tumor cells and the requirement for HLA matching in allogeneic settings remain significant hurdles in clinical application (Taylor et al., 2015, Phil. Trans. R. Soc. B).

Other names

EBV-HLA complexEBV-peptide-MHC complexEpstein-Barr virus-associated tumor antigensEBV-derived MHC-presented peptides

T-cell receptor (TCR) mediated recognition of viral peptides presented on MHC molecules, leading to cytotoxic T-lymphocyte (CTL) activation and lysis of EBV-infected cells (Bollard & Heslop, 2016, Blood).