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

The Epstein-Barr virus nuclear antigen 1 (EBNA1) peptide-major histocompatibility complex (pMHC) is a therapeutic target found on the surface of cells latently infected with Epstein-Barr virus (EBV). EBNA1 is a multifunctional protein essential for the replication and maintenance of the EBV episome, making it a consistent marker for EBV-associated malignancies such as Nasopharyngeal carcinoma and Burkitt lymphoma (PMID: 21937657). Because EBNA1 is an intracellular protein, it is not accessible to standard monoclonal antibodies; however, it is processed and presented on the cell surface as a peptide complexed with Major Histocompatibility Complex (MHC) molecules, particularly HLA-A*02:01 (PMID: 31434706). This pMHC complex can be targeted by T-cell receptor (TCR)-engineered T cells or TCR-like antibodies that recognize the specific viral peptide in the context of the host's HLA (PMID: 26034163). These therapies aim to selectively destroy EBV-positive tumor cells while sparing healthy tissue. Clinical challenges include the requirement for HLA-matching and the potential for immune escape through the downregulation of MHC molecules on the surface of cancer cells.

Other names

EBNA1-HLA complexEBNA1-MHC complexEBNA1 peptide-HLA-A*02:01 complexEBV EBNA1-pMHCEpstein-Barr virus nuclear antigen 1-HLA-A2 complex

MHC-restricted T-cell mediated cytotoxicity