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Cytomegalovirus (CMV) phosphoprotein 65 (pp65) and immediate-early protein 1 (IE-1) are immunodominant viral antigens that play a critical role in the host immune response (Stern et al., 2019). During infection, these proteins are proteolytically processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules. These peptide-HLA (pHLA) complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate the lysis of the infected cell to control viral spread (Wills et al., 1996). In clinical settings, particularly following hematopoietic stem cell or solid organ transplantation, these pHLA complexes are primary targets for immunotherapies designed to restore CMV-specific immunity. Current therapeutic approaches include the adoptive transfer of donor-derived or off-the-shelf CMV-specific T cells, as well as vaccines like Triplex that encode these antigens to stimulate endogenous T-cell expansion (City of Hope, 2022). Monitoring the presence of these complexes and the corresponding T-cell frequency is essential for managing CMV reactivation and ensuring the safety and efficacy of T-cell-based interventions (AlloVir, 2023).
Targeted recognition by T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) mediated apoptosis of CMV-infected cells
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