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The CMV pp65-derived epitope (NLVPMVATV) presented on HLA-A*02:01 is a critical immunological target for managing Human Cytomegalovirus (HCMV) infections and associated pathologies (Wills et al., 1996, PubMed: 8676462). The pp65 protein, encoded by the UL83 gene, is a major structural component of the CMV tegument and a primary target for the host's cellular immune response (UniProt: P06725). The specific peptide sequence spanning amino acids 495-503 is highly immunogenic and is presented by the HLA-A*02:01 molecule, one of the most prevalent MHC class I alleles in the human population (Diamond et al., 1997, PubMed: 9213134). This peptide-MHC complex is a focal point for the development of adoptive T-cell therapies, TCR-engineered T cells, and peptide-based vaccines aimed at restoring CMV-specific immunity in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation. Therapeutic strategies include the use of the Triplex vaccine (NCT02506933) and various CMV-specific cytotoxic T-lymphocyte products. Beyond viral infection, this target has been investigated in the context of certain cancers, most notably glioblastoma, where CMV antigens are frequently detected in tumor cells. Therapeutic interventions targeting this complex work by enabling CD8+ T cells to recognize and eliminate cells expressing the viral epitope, thereby controlling viral replication or tumor growth.
Recognition by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the targeted lysis of CMV-infected or antigen-expressing cells.
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