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

Epstein-Barr virus-derived peptide–Major Histocompatibility Complex class I (EBV pMHC I) complexes are molecular assemblies consisting of viral peptide fragments, such as those from EBNA or LMP proteins, bound within the groove of host MHC class I molecules (Hislop et al., 2007, PubMed: 17591595). These complexes are presented on the surface of EBV-infected cells and EBV-associated malignancies, including nasopharyngeal carcinoma and post-transplant lymphoproliferative disorder (PTLD) (Taylor et al., 2015, PubMed: 25703530). The primary biological role of these complexes is to serve as ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response to destroy the presenting cell (Long et al., 2011, PubMed: 21149605). In therapeutic development, EBV pMHC I complexes are the primary targets for adoptive T-cell therapies and TCR-engineered cells, which aim to overcome immune evasion in EBV-driven cancers. For instance, tabelecleucel is an allogeneic T-cell therapy designed to recognize these complexes in patients with EBV+ PTLD (Prockop et al., 2020, PubMed: 32015549). Challenges in targeting these complexes include the high polymorphism of HLA molecules and the potential for off-target cross-reactivity with similar self-peptides.

Other names

EBV peptide-HLA class I complexEpstein-Barr virus antigen-MHC complexEBV-specific pMHCEBV pMHC

Recognition by T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to targeted lysis of EBV-infected or transformed cells.