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

The Cytomegalovirus phosphoprotein 65 (pp65) peptide-MHC class I complex is a primary immunological target for the cellular immune response against Human Cytomegalovirus (HCMV) (UniProt: P06725). pp65, also known as UL83, is a major tegument protein that is processed by the proteasome into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (PubMed: 12142847). This presentation allows CD8+ cytotoxic T lymphocytes (CTLs) to recognize and eliminate infected cells, making it a cornerstone of natural viral control. In clinical practice, this complex is targeted to prevent or treat CMV disease in immunocompromised individuals, particularly hematopoietic stem cell transplant recipients, through the adoptive transfer of pp65-specific T cells (PubMed: 30711031). Beyond infectious disease, the presence of pp65 in certain tumors, such as glioblastoma multiforme, has positioned this pMHC complex as a novel target for cancer immunotherapy (PubMed: 11929810). Therapeutic interventions include peptide vaccines, such as PepVax, and viral vector vaccines like Triplex, which aim to expand the pool of pp65-reactive T cells (ClinicalTrials.gov: NCT02396134). Additionally, T-cell receptor (TCR) engineered therapies are being developed to specifically bind these peptide-MHC complexes with high affinity (PubMed: 19155474). Monitoring the efficacy of these treatments often involves measuring pp65-specific T-cell frequencies using MHC tetramer staining or ELISpot assays.

Other names

CMV pp65 antigenUL83 peptide-HLA complexpp65-derived T-cell epitopeHLA-A*02:01/NLVPMVATV complexHuman cytomegalovirus phosphoprotein 65

Recognition by T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the activation of immune effector functions and lysis of cells presenting the viral peptide.