Epstein-Barr nuclear antigen 1 peptide–Human leukocyte antigen complex (EBNA1-HLA complex)

The Epstein-Barr nuclear antigen 1 (EBNA1) peptide–Human leukocyte antigen (HLA) complex is a critical immunological target found on the surface of cells infected with Epstein-Barr virus (EBV), particularly in EBV-associated malignancies. EBNA1 is a multifunctional viral protein necessary for the replication and persistence of the EBV episome, and it is the only viral protein expressed in all EBV-related latency patterns (Sivachandran et al., 2012, J Virol). Since EBNA1 is an intracellular protein, it cannot be targeted by traditional antibodies; however, its degradation products are processed and presented as peptides by HLA class I molecules on the cell surface (Taylor et al., 2004, J Exp Med). These peptide-MHC complexes provide a unique molecular signature for EBV-positive tumor cells, such as those in nasopharyngeal carcinoma and certain lymphomas. Therapeutic strategies targeting these complexes include T-cell receptor (TCR)-engineered T-cells and TCR-like antibodies, such as ET1402L1, which are designed to recognize the specific peptide-HLA configuration with high affinity (Liu et al., 2017, JCI Insight). This approach aims to induce selective apoptosis of malignant cells while minimizing damage to healthy, non-infected tissues that do not present the viral peptide.

Other names

EBNA1-MHC complexEBNA1-HLA-A*02:01 complexEBV-specific peptide-MHCEpstein-Barr nuclear antigen 1-MHC class I complexEBNA1 pMHC

Targeted cell lysis via T-cell receptor (TCR) recognition or TCR-like antibody-mediated recruitment of effector cells and induction of apoptosis.