Epstein-Barr virus latency antigens presented on human leukocyte antigen (EBV latency antigen-HLA complex)

Epstein-Barr virus (EBV) latency antigens presented on human leukocyte antigen (HLA) represent a critical class of therapeutic targets for EBV-associated malignancies and lymphoproliferative disorders (Young & Rickinson, 2004). EBV establishes a persistent, latent infection in B cells and epithelial cells, expressing a specific subset of proteins known as latent membrane proteins (LMP1, LMP2A, LMP2B) and EBV nuclear antigens (EBNA1, EBNA2, EBNA3A-C). These proteins are proteolytically processed into short peptides and presented on the cell surface by HLA Class I and Class II molecules, where they serve as epitopes for T-cell recognition (Haque et al., 2007). In EBV-driven cancers such as Nasopharyngeal Carcinoma (NPC), Hodgkin Lymphoma, and Post-Transplant Lymphoproliferative Disorder (PTLD), these peptide-HLA complexes are the primary targets for adoptive cellular therapies, including EBV-specific T-cells (EBVSTs) and TCR-engineered T-cells (Prock et al., 2023). Drugs like tabelecleucel utilize this mechanism by providing HLA-matched, EBV-specific cytotoxic T-lymphocytes that recognize these viral antigens to eliminate infected or malignant cells. The therapeutic challenge lies in the diversity of HLA alleles across populations and the potential for viral immune evasion through the downregulation of HLA expression or antigen processing machinery.

Other names

EBV-HLA complexEBV peptide-MHC complexEBV latent membrane proteins presented on MHCEBV nuclear antigens presented on MHCEBV-specific T-cell targetsEpstein-Barr virus pMHC

Recognition of viral peptide-HLA complexes by T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) mediated lysis of infected cells.