Epstein-Barr virus BamHI-A rightward frame 1-derived peptide–Human leukocyte antigen complex (EBV BARF1–HLA complex)

The Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is a viral oncogene and immunomodulator primarily expressed in Latency type II/III EBV-associated malignancies, including nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBVaGC). BARF1-derived peptides are processed intracellularly and presented on the cell surface via Human Leukocyte Antigen (HLA) Class I and Class II molecules, forming specific peptide-HLA (pHLA) complexes. These complexes are considered ideal therapeutic targets because BARF1 expression is restricted to EBV-infected malignant cells and is absent in healthy tissues, minimizing off-target risks. Therapeutic interventions, such as T-cell receptor (TCR) engineered T-cells (TCR-T) and therapeutic vaccines, are being developed to recognize these pHLA complexes and induce a targeted cytotoxic immune response. Additionally, since the BARF1 protein itself acts as a decoy receptor for colony-stimulating factor 1 (CSF-1) to suppress macrophage activity, targeting the cells presenting BARF1 peptides may also help alleviate local immunosuppression within the tumor microenvironment.

Other names

BARF1-HLA complexEBV BARF1 pMHCBamHI-A rightward frame 1 peptide-HLA complexBARF1 peptide-MHC complex

T-cell receptor-mediated recognition of the peptide-HLA complex leading to cytotoxic T-lymphocyte activation and lysis of the target cell.