Epstein-Barr virus BZLF1-derived peptide–Major Histocompatibility Complex (EBV BZLF1-pMHC)

The Epstein-Barr virus (EBV) BZLF1-derived peptide–Major Histocompatibility Complex (MHC) is a specialized molecular target used in the immunotherapy of EBV-associated diseases. BZLF1 (also known as Zta or ZEBRA) is an immediate-early viral protein that acts as the master transcription factor for the switch from latent to lytic EBV infection (UniProt: P03206). During the lytic phase, BZLF1 is processed into peptides, such as the immunodominant RAKFKQLL epitope, which are then presented on the cell surface by MHC Class I molecules, most commonly HLA-A*02:01 (PubMed: 9247449). These complexes serve as the primary recognition signal for CD8+ cytotoxic T cells, which identify and kill infected cells to control viral spread. In clinical applications, these pMHC complexes are targeted by engineered T-cell receptor (TCR) therapies and TCR-like antibodies to treat EBV-positive malignancies like nasopharyngeal carcinoma and post-transplant lymphoproliferative disorders (PubMed: 30309861). The therapeutic challenge lies in the high degree of HLA polymorphism, requiring treatments to be matched to the patient's specific MHC profile. Additionally, there is a risk of cross-reactivity with similar human self-peptides, which can lead to off-target toxicity (PubMed: 36543865). Targeting BZLF1 is particularly effective because it is expressed very early in the viral lytic cycle, allowing for the elimination of cells before new virions are produced.

Other names

BZLF1-HLA complexZta-MHC complexZEBRA-MHC complexHLA-A*02:01/RAKFKQLL complexEBV lytic antigen-MHC complex

T-cell receptor-mediated cytotoxicity