Human cytomegalovirus phosphoprotein 65 peptide-HLA class I complex (HCMV pp65-HLA-I)

The Human cytomegalovirus (HCMV) phosphoprotein 65 (pp65) peptide presented by HLA class I is a primary immunological target for the management of CMV infections and certain malignancies. pp65, also known as UL83, is the most abundant tegument protein of HCMV and is highly immunogenic (UniProt P06725). During viral replication or in pp65-expressing tumor cells, the protein is processed into short peptides that are presented on the cell surface by HLA class I molecules, such as the immunodominant NLVPMVATV peptide presented by HLA-A*02:01 (PubMed: 8551620). This peptide-MHC complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate cell lysis. In clinical practice, this target is utilized for adoptive T-cell therapies, where CMV-specific T cells are infused into immunocompromised patients to prevent or treat CMV disease (PubMed: 25762174). Additionally, pp65-targeted vaccines and TCR-engineered T cells are being investigated for their efficacy against glioblastoma, where pp65 is frequently expressed (PubMed: 24443442). The specificity of the interaction between the TCR and the pp65-HLA complex allows for precise targeting, although it requires matching the patient's HLA type. Therapeutic challenges include potential immune evasion by the virus through the downregulation of HLA molecules and the risk of cytokine release syndrome during intensive T-cell therapy.

Other names

CMV pp65-MHC class I complexUL83 peptide-HLA complexpp65-HLA-A*02:01HCMV pp65 antigenNLVPMVATV-HLA-A*02:01 complex

Recognition of the peptide-HLA complex by endogenous or adoptively transferred T-cell receptors (TCRs), leading to the activation of cytotoxic signaling pathways and apoptosis of the target cell.