Cytomegalovirus 65 kDa phosphoprotein peptide–MHC class I complex (CMV pp65–MHC I complex)

The Cytomegalovirus 65 kDa phosphoprotein (pp65) peptide–MHC class I complex is a primary immunological target for the management of Human Cytomegalovirus (HCMV) infections, particularly in immunocompromised individuals (PubMed: 15604141). pp65, encoded by the UL83 gene, is the most abundant tegument protein of the virus and serves as a dominant antigen for CD8+ T-cell responses (UniProt: P06725). During the viral life cycle, pp65 is processed into short peptides, such as the well-characterized NLVPMVATV epitope, which are presented on the cell surface by MHC class I molecules, most frequently HLA-A*02:01 (PubMed: 10833265). This complex is recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, which then execute the destruction of the infected cell. In the context of drug development, this complex is targeted by adoptive T-cell therapies, TCR-engineered T cells, and peptide-based vaccines like CMVPepVax to restore antiviral immunity in transplant recipients (NCT02396134). The specificity of the interaction between the TCR and the pMHC complex is a key focus for avoiding off-target effects and ensuring therapeutic efficacy.

Other names

pp65-pMHCUL83-HLA complexCMV pp65-HLA-A*02:01 complexHuman cytomegalovirus phosphoprotein 65 peptide-MHC complex

T-cell receptor-mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and targeted cell lysis.