Cytomegalovirus 65 kDa phosphoprotein (pp65) peptides presented by HLA class I (CMV pp65-HLA class I complex)

The Cytomegalovirus 65 kDa phosphoprotein (pp65), encoded by the UL83 gene, is the primary tegument protein of Human Cytomegalovirus (HCMV) and serves as the immunodominant target for the host immune response (UniProt P06725). During infection, pp65 is processed by the proteasome into short peptides, which are then transported into the endoplasmic reticulum and loaded onto HLA class I molecules for presentation on the cell surface (PubMed PMID: 9213141). This peptide-MHC complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T-lymphocytes, making it a critical focal point for cellular immunity. In immunocompromised individuals, such as hematopoietic stem cell or solid organ transplant recipients, the failure of this T-cell recognition leads to CMV reactivation and severe clinical complications (PubMed PMID: 24027103). Consequently, the pp65-HLA complex is a major target for adoptive cell therapies, including virus-specific T-cells (VSTs) and TCR-engineered T-cells, as well as prophylactic vaccines designed to boost CMV-specific immunity. Therapeutic strategies often focus on specific high-prevalence alleles, such as HLA-A*02:01, which presents the well-characterized NLVPMVATV peptide (PubMed PMID: 10438932). Monitoring the presence and frequency of T-cells reactive to this complex is a standard biomarker for assessing a patient's ability to control viral replication.

Other names

pp65-MHC class I complexUL83 peptide-HLA complexCMV pp65/HLA-A*02:01Cytomegalovirus tegument protein pp65 peptidespMHC complex (CMV pp65)

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ cytotoxic T-lymphocytes, triggering the release of perforins and granzymes to induce apoptosis in CMV-infected cells.