Epstein-Barr virus nuclear antigen 1-derived peptide–major histocompatibility complex (EBNA1-pMHC)

Epstein-Barr virus nuclear antigen 1-derived peptide–major histocompatibility complex (EBNA1-pMHC) refers to the cell-surface presentation of EBNA1-derived peptides by MHC (HLA) molecules. EBNA1 is a multifunctional viral protein essential for the replication, segregation, and maintenance of the EBV episome within host cells. Unlike many other viral proteins, EBNA1 is expressed in all EBV-associated malignancies, including Nasopharyngeal Carcinoma (NPC), Hodgkin lymphoma, and Burkitt lymphoma, making its pMHC complex a critical target for immunotherapy. In a therapeutic context, these complexes are targeted by T-cell receptor (TCR) engineered T-cells or TCR-like antibodies that recognize the specific peptide-HLA configuration. Because EBNA1 is often the only viral protein expressed in certain latency stages (Latency I), targeting the EBNA1-pMHC complex allows the immune system to identify and eliminate latently infected cells and EBV-driven tumor cells that would otherwise remain invisible. Current research focuses on identifying high-affinity TCRs and bispecific molecules that can overcome the low-density presentation of these complexes on the tumor cell surface.

Other names

EBNA1-HLA complexEBNA1 peptide-MHCEBNA1-MHC class I complexEBNA1-derived pMHC

Targeting of EBNA1-pMHC complexes by engineered T-cells or antibodies induces direct lysis of EBV-infected or malignant cells through T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC).