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JC polyomavirus (JCV) large T antigen-derived peptide–HLA complexes are molecular assemblies presented on the surface of cells infected with the JC polyomavirus. The large T antigen (LTA) is a non-structural viral protein essential for the replication of the viral genome and the orchestration of the lytic cycle (Shishido-Hara, 2010). Peptides derived from the LTA are processed and loaded onto Human Leukocyte Antigen (HLA) molecules, typically MHC Class I, for presentation to the immune system (Du Pasquier et al., 2003). These complexes serve as the primary target for CD8+ cytotoxic T lymphocytes, which are crucial for controlling JCV infection and preventing its progression into Progressive Multifocal Leukoencephalopathy (PML) (Koralnik, 2006). In clinical settings, these complexes are targeted by adoptive immunotherapies, including virus-specific T cells (VSTs) and TCR-engineered cells, designed to restore cellular immunity in immunocompromised patients (Muftuoglu et al., 2018). The interaction between the T-cell receptor and the peptide-HLA complex is highly specific, and its failure is a hallmark of PML pathogenesis (Lima et al., 2007).
Recognition by antigen-specific T-cell receptors (TCRs) on CD8+ T cells, leading to the release of cytotoxic granules (perforin and granzymes) and apoptosis of the JCV-infected cell (Du Pasquier et al., 2003; Muftuoglu et al., 2018).
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