Human leukocyte antigen-restricted Epstein-Barr virus BZLF1-derived peptide–major histocompatibility complex (HLA-EBV-BZLF1-pMHC) (HLA-EBV-BZLF1-pMHC)

Human leukocyte antigen (HLA)-restricted Epstein-Barr virus (EBV) BZLF1-derived peptide–major histocompatibility complex (pMHC) is a molecular assembly consisting of a peptide fragment from the EBV BZLF1 protein bound to an HLA molecule on the cell surface (UniProt P03206). BZLF1, also known as Zta or ZEBRA, is an immediate-early protein that functions as a transcription factor to trigger the transition from latent to lytic EBV infection (PMID: 25609774). These complexes are crucial for the immune system's ability to detect and eliminate EBV-infected cells, as they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (PMID: 7514803). In therapeutic applications, these pMHC complexes are targeted by adoptive T-cell therapies, including EBV-specific T cells (e.g., Tabelecleucel) and TCR-engineered T cells, to treat EBV-associated malignancies like nasopharyngeal carcinoma and post-transplant lymphoproliferative disorder (PTLD) (PMID: 31533978). Because BZLF1 is expressed very early during viral reactivation, targeting these complexes allows for the destruction of reservoir cells before the production of new viral particles. Therapeutic challenges include the potential for HLA downregulation by tumors to evade immune detection and the need for precise HLA matching between the therapy and the patient.

Other names

EBV BZLF1 peptide-MHC complexHLA-BZLF1 complexZEBRA peptide-HLA complexZta peptide-MHCEBV lytic antigen pMHCRAKFKQLL-HLA-B*08:01 complex

Recognition by T-cell receptors (TCRs) on CD8+ cytotoxic T cells, leading to the targeted lysis of EBV-infected or malignant cells presenting the BZLF1-derived peptide.