Epstein-Barr virus nuclear antigen 1 peptide presented on MHC class I (EBNA1-pMHC-I)

Epstein-Barr virus nuclear antigen 1 (EBNA1) is a DNA-binding protein essential for the maintenance, replication, and transcription of the EBV genome (UniProt P03211). It is the only viral protein consistently expressed in all EBV-associated malignancies, including Nasopharyngeal carcinoma, Burkitt lymphoma, and Hodgkin lymphoma (PubMed: 21442048). Although EBNA1 contains a glycine-alanine repeat (GAr) domain that inhibits its proteasomal degradation to evade immune detection, specific EBNA1-derived peptides are successfully processed and presented on MHC class I molecules (PubMed: 15604275). These peptide-MHC (pMHC) complexes serve as highly specific targets for CD8+ cytotoxic T cells, enabling the selective elimination of EBV-infected or transformed cells. Current therapeutic strategies targeting the EBNA1-pMHC complex include TCR-engineered T cells, allogeneic T-cell therapies like Tabelecleucel, and peptide-based vaccines (PubMed: 30305451). Because EBNA1 is a foreign viral protein, it represents an attractive target for immunotherapy with a potentially lower risk of off-target toxicity compared to self-antigens.

Other names

EBNA1-HLA complexEBNA1 peptide-MHC complexEBV EBNA1-MHC-IEpstein-Barr virus nuclear antigen 1-derived peptide-MHC class I complex

Targeting of EBNA1-derived peptides presented on MHC class I molecules enables CD8+ cytotoxic T cells or engineered immune cells to recognize and lyse EBV-infected or malignant cells via T-cell receptor (TCR) engagement.