Epstein-Barr virus latency antigen-derived peptide–human leukocyte antigen complexes (EBV pHLA complexes)

Epstein-Barr virus (EBV) latency antigen-derived peptide–human leukocyte antigen (HLA) complexes are molecular assemblies on the surface of infected cells that present fragments of viral proteins to the immune system (Young et al., 2016). These complexes consist of short peptides derived from EBV latent proteins—such as EBNA1, LMP1, and LMP2—bound to the groove of HLA Class I molecules (Bollard & Heslop, 2016). They serve as the primary recognition signal for CD8+ cytotoxic T lymphocytes, which identify and destroy cells expressing these viral markers. In EBV-associated cancers like Nasopharyngeal Carcinoma and Post-Transplant Lymphoproliferative Disorder (PTLD), these pHLA complexes are targeted by immunotherapies, including adoptive T-cell transfers and engineered TCR-T cells (Prockop et al., 2020). Because these targets are derived from non-self viral proteins, they offer high specificity for infected or malignant cells, minimizing damage to healthy tissues (Smith et al., 2015). However, the effectiveness of these therapies depends on the patient's HLA type and the ability of the tumor to maintain antigen presentation under selective pressure (Tierney et al., 2015).

Other names

EBV peptide-MHC complexesEBV pMHCEBV-specific pHLAEBNA/LMP peptide-HLA complexesEBV-specific peptide-HLA complexes

Recognition of viral peptides presented on HLA molecules by T-cell receptors (TCRs) or TCR-mimetic antibodies, which triggers the activation of cytotoxic T cells and subsequent lysis of the EBV-infected target cell.