Cytomegalovirus phosphoprotein 65-derived peptide–Major Histocompatibility Complex (CMV pp65-pMHC) (CMV pp65-pMHC)

Cytomegalovirus (CMV) pp65-derived peptide–MHC complexes are immunodominant molecular assemblies formed when fragments of the viral phosphoprotein 65 (pp65) are presented on the surface of host cells by Major Histocompatibility Complex (MHC) class I molecules (Kactus Bio, 2024; JPT Peptide Technologies, 2024). The pp65 protein is the most abundant tegument protein of CMV and serves as a primary target for the host's cellular immune response, accounting for a significant portion of the CMV-specific CD8+ T-cell repertoire (NIH, 2021; MDPI, 2021). The most extensively studied epitope within this complex is the NLVPMVATV peptide presented by the HLA-A*02:01 allele, which is highly prevalent in the human population (NIH, 2025; MDPI, 2021). These complexes are essential for the recognition of CMV-infected cells by CD8+ cytotoxic T lymphocytes (CTLs), which then mediate cell lysis to control viral replication and maintain latency (NIH, 1994; SciSpace, 2024). In clinical settings, these complexes are targeted to prevent or treat CMV reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (GenScript, 2024; NIH, 2022). Furthermore, because pp65 is expressed in certain malignancies like glioblastoma but not in healthy brain tissue, these pMHC complexes are also being investigated as targets for cancer immunotherapy (NIH, 2025; MDPI, 2022). Therapeutic approaches targeting these complexes include peptide-based vaccines like Triplex and PepVax, adoptive transfer of CMV-specific T cells, and engineered TCR-T or TCR-like antibody therapies (NCI, 2024; NIH, 2015).

Other names

pCMV-pp65/HLA-A2HLA-A*02:01/pp65(495-503) complexCMV pp65 peptide-MHC complexpp65-pMHCNLVPMVATV/HLA-A*02:01 complexHuman cytomegalovirus pp65-derived peptide–MHC complex

The target serves as a ligand for T-cell receptors (TCRs) or engineered TCR-like molecules. Recognition of the complex by these receptors triggers the activation of cytotoxic T lymphocytes (CTLs), leading to the release of perforin and granzymes and the subsequent lysis of the target cell (e.g., a CMV-infected cell or a pp65-expressing tumor cell).