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Epstein-Barr virus nuclear antigen (EBNA)-derived peptide–major histocompatibility complex (MHC) refers to the presentation of viral protein fragments on the surface of EBV-infected cells (Amiri et al., 2021, Front Immunol). During latent infection, the virus expresses several nuclear antigens, such as EBNA1, EBNA2, and the EBNA3 family, which are processed into short peptides and loaded onto MHC Class I or II molecules (Taylor et al., 2015, J Gen Virol). These complexes serve as the primary recognition signals for the host's cellular immune response, particularly cytotoxic T lymphocytes (CTLs). In EBV-associated malignancies like nasopharyngeal carcinoma and post-transplant lymphoproliferative disorder (PTLD), these pMHC complexes are utilized as highly specific therapeutic targets (Prockop et al., 2020, J Clin Invest). Modern immunotherapies, including the approved allogeneic T-cell therapy tabelecleucel and experimental TCR-engineered cells, are designed to bind these specific EBNA-pMHC combinations to induce targeted cell death (Haque et al., 2007, Lancet Oncol). Furthermore, the interaction between EBNA1-derived peptides and specific HLA alleles has been strongly linked to the pathogenesis of multiple sclerosis (Bjornevik et al., 2022, Science).
Targeted recognition of viral epitopes by T-cell receptors (TCRs) or engineered immune cells, leading to the release of perforins and granzymes that induce apoptosis in the target cell (Amiri et al., 2021, Front Immunol).
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