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Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the primary tegument protein of Human Cytomegalovirus (HCMV) and serves as the immunodominant target for the host's CD8+ cytotoxic T-lymphocyte (CTL) response [1, 2]. During infection, pp65 is processed into short peptide epitopes that are presented on the cell surface by matched HLA class I molecules [3]. These HLA-peptide complexes are recognized by specific T-cell receptors (TCRs), which triggers an effector response involving the release of cytotoxins like granzymes and perforins to eliminate the infected cell. While the NLVPMVATV epitope (restricted by HLA-A*02:01) is the most frequently targeted in research, a wide variety of other epitopes restricted by diverse HLA-A, -B, and -C alleles are essential for comprehensive immune protection across different populations [3, 4]. In clinical practice, these epitopes are utilized as targets for adoptive T-cell therapies and vaccines, particularly to prevent or treat CMV reactivation in immunocompromised patients such as hematopoietic stem cell transplant recipients [5]. Monitoring the frequency and functionality of T cells specific to these epitopes via assays like ELISPOT or MHC multimer staining provides critical biomarkers for assessing immune reconstitution and therapeutic efficacy [4]. Citations: [1] UniProt P06725; [2] Wills et al., 1996 (J. Virol); [3] Sylwester et al., 2005 (J. Exp. Med.); [4] Gratama et al., 2001 (Blood); [5] ClinicalTrials.gov (NCT02313857).
Recognition of the HLA-peptide complex by CD8+ T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) activation, secretion of pro-inflammatory cytokines (IFN-gamma, TNF-alpha), and direct lysis of CMV-infected cells.
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