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Adenovirus structural protein-derived peptide–Human Leukocyte Antigen (HLA) complexes are molecular assemblies found on the surface of cells infected with Adenovirus. These complexes consist of a viral peptide fragment, typically derived from highly conserved structural proteins like Hexon, Penton base, or Fiber, bound within the groove of an HLA class I or class II molecule (PubMed: 25609113). Their primary biological function is to signal the presence of an intracellular pathogen to the immune system, specifically acting as the ligand for T-cell receptors (TCRs) on cytotoxic CD8+ T cells (PubMed: 15140913). In the context of disease, these complexes are critical for the clearance of adenovirus infections, which can be fatal in immunocompromised patients, such as those undergoing hematopoietic stem cell transplantation (PubMed: 21670471). Therapeutic interventions targeting these complexes include the adoptive transfer of virus-specific T-cells (VSTs) or the development of TCR-engineered T-cells that recognize specific immunodominant epitopes like the Hexon-derived "TYFSLNNKF" peptide (PubMed: 19074378). The efficacy of these treatments is highly dependent on the patient's HLA genotype and the conservation of the viral epitope across different adenovirus serotypes. Challenges in targeting these complexes include viral mechanisms that downregulate HLA expression to evade immune detection and the potential for cross-reactivity with self-peptides (PubMed: 12692221).
Recognition of the peptide-HLA complex by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering the release of perforin and granzymes to induce apoptosis in the infected cell.
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