Epstein-Barr virus nuclear antigen 3 peptide-Major Histocompatibility Complex (EBNA3-pMHC) (EBNA3-pMHC)

Epstein-Barr virus nuclear antigen 3 (EBNA3) peptide-Major Histocompatibility Complex (pMHC) complexes are molecular assemblies presented on the surface of EBV-infected cells, primarily B-lymphocytes. These complexes consist of short peptide fragments derived from the EBNA3A, 3B, or 3C proteins bound to HLA class I molecules (Young et al., 2016). The EBNA3 proteins are essential for the virus's ability to transform B cells and maintain long-term latent infection by modulating host gene expression. Because these pMHC complexes are unique to infected cells, they serve as highly specific targets for the host's cytotoxic CD8+ T-cell response. In clinical settings, these complexes are targeted by adoptive T-cell therapies like tabelecleucel, which utilizes EBV-specific T cells to treat EBV-associated post-transplant lymphoproliferative disorder (Prockop et al., 2020). Furthermore, engineered T-cell receptor (TCR) therapies and bispecific molecules are being developed to recognize specific EBNA3-pMHC combinations, such as those restricted by HLA-A*02:01, to treat EBV-related malignancies (Bentzen & Hadrup, 2017). The therapeutic goal is to induce selective apoptosis of EBV-positive cells while minimizing damage to healthy, non-infected tissues. Recent research has also highlighted the potential role of EBV-specific immune responses in the pathogenesis of multiple sclerosis, further expanding the clinical relevance of these targets (Bjornevik et al., 2022).

Other names

EBV EBNA3-HLA complexEBNA3A/B/C peptide-MHCEBNA3-MHC class I complexEpstein-Barr virus EBNA3-MHC

Recognition by T-cell receptors (TCRs) on cytotoxic T lymphocytes leading to targeted lysis of EBV-infected cells (Prockop et al., 2020).