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The HLA-A*02:01–LMP2 EBV peptide–HLA class I complex is a specialized antigen-presenting structure consisting of the HLA-A*02:01 heavy chain, beta-2 microglobulin, and a specific immunodominant peptide (typically CLGGLLTMV) derived from the Latent Membrane Protein 2 (LMP2) of the Epstein-Barr Virus (EBV). This complex is expressed on the surface of cells latently infected with EBV and is a hallmark of EBV-associated malignancies, including nasopharyngeal carcinoma and certain types of Hodgkin and non-Hodgkin lymphomas. Its primary biological role is to display viral fragments to the immune system, specifically to CD8+ cytotoxic T lymphocytes, to trigger an antiviral response. In oncology, this complex is a high-priority therapeutic target because it allows for the precise identification of tumor cells harboring the viral genome. Current therapeutic strategies include the development of TCR-engineered T-cell (TCR-T) therapies and TCR-like bispecific molecules that mimic the natural recognition mechanism of the immune system to selectively eliminate cancer cells while sparing healthy, non-infected tissue.
Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce selective lysis of EBV-infected or EBV-transformed cells through the release of perforins and granzymes.
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