Epstein-Barr virus antigen-Major Histocompatibility Complex (EBV pMHC)

Epstein-Barr virus (EBV) antigens presented on the Major Histocompatibility Complex (MHC) of EBV-positive tumor cells serve as highly specific targets for cancer immunotherapy (Taylor et al., 2015, Nature Reviews Immunology). In EBV-associated malignancies, such as nasopharyngeal carcinoma and post-transplant lymphoproliferative disorder (PTLD), the virus maintains a latency program where specific viral proteins like EBNA1, LMP1, and LMP2 are expressed (Young et al., 2016, Nature Reviews Cancer). These proteins are proteolytically processed into short peptides and presented on the cell surface by HLA molecules, forming peptide-MHC (pMHC) complexes. These complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T-lymphocytes, which then initiate the destruction of the tumor cell. Therapeutic interventions, including adoptive T-cell therapies like tabelecleucel (Ebvallo) and TCR-engineered T-cells, specifically exploit these pMHC targets to achieve tumor-selective killing (Prockop et al., 2020, JCI). Because these viral antigens are not present in healthy human cells, they provide a narrow therapeutic window with reduced risk of systemic toxicity compared to traditional chemotherapy. However, the effectiveness of these therapies depends on the patient's HLA type and the continued expression of MHC molecules by the tumor (Bollard & Heslop, 2016, Blood). Monitoring EBV DNA levels and EBER expression is crucial for identifying eligible patients and assessing treatment response (Kimura et al., 2013, Frontiers in Microbiology).

Other names

EBV peptide-HLA complexEBV-associated tumor antigensEBV-specific pMHCEpstein-Barr virus-derived HLA-restricted peptides

Recognition of viral peptide-MHC complexes by T-cell receptors (TCRs) on cytotoxic T-lymphocytes (CTLs), leading to the release of perforin and granzymes and subsequent apoptosis of the EBV-positive tumor cell (Hislop et al., 2007, Annual Review of Immunology).