Epstein-Barr virus antigen–Human leukocyte antigen complex (EBV-HLA complex)

The Epstein-Barr virus (EBV) antigen–Human leukocyte antigen (HLA) complex consists of viral peptides derived from EBV latent or lytic proteins presented on the surface of tumor cells by MHC Class I or II molecules. In EBV-associated malignancies, such as nasopharyngeal carcinoma and various lymphomas, the tumor cells constitutively express specific viral proteins like EBNA1, LMP1, and LMP2, which are processed into peptides and displayed by HLA molecules. These complexes serve as highly specific neoantigens because they are absent from healthy, non-infected tissues, making them ideal targets for immunotherapy. Therapeutic strategies targeting these complexes include adoptive T-cell therapies, such as EBV-specific cytotoxic T-lymphocytes (CTLs) and TCR-engineered T-cells, which recognize the pMHC through their native or recombinant T-cell receptors. The most prominent clinical success in this area is Tabelecleucel, an allogeneic T-cell therapy approved for EBV-positive post-transplant lymphoproliferative disorder. Because the recognition is HLA-restricted, patient selection requires matching the therapy to the patient's specific HLA haplotype (e.g., HLA-A*02:01). While highly effective, challenges include potential immune evasion by the tumor through the loss of HLA expression and the risk of inflammatory side effects like cytokine release syndrome.

Other names

EBV peptide-MHC complexEBV pMHCEBV-specific HLA-peptide complexEpstein-Barr virus-associated tumor antigen complexEBV-restricted HLA complex

T-cell receptor (TCR) mediated recognition leading to T-cell activation and direct lysis of EBV-infected tumor cells.