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The Cytomegalovirus (CMV) pp65 peptide NLVPMVATV presented by HLA-A*0201 is a major immunodominant epitope derived from the UL83 (pp65) tegument protein of Human Betaherpesvirus 5 (UniProt: P06725). This peptide-MHC (pMHC) complex serves as a critical target for the cellular immune system, specifically for CD8+ cytotoxic T lymphocytes (CTLs) in individuals carrying the HLA-A*02:01 allele (PubMed: 8805300). In immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients, the failure of the immune system to recognize this complex leads to uncontrolled CMV replication and life-threatening disease (PubMed: 22535000). Therapeutic interventions targeting this complex include adoptive cell therapies like posoleucel (Viralym-M) and other CMV-specific T-cell products which recognize the NLVPMVATV epitope to restore viral immunity (ClinicalTrials.gov: NCT04354311). Additionally, T-cell receptor (TCR)-engineered T cells and TCR-like antibodies are being developed to provide high-specificity targeting of CMV-infected cells (PubMed: 31434705). Monitoring the frequency of T cells specific to this epitope using MHC tetramers is a standard biomarker for assessing a patient's functional immunity against CMV.
Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on cytotoxic T cells, leading to the formation of an immunological synapse and subsequent lysis of the infected cell.
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