CMV pp65 peptide–MHC class I complexes (CMV pp65 pMHC)

CMV pp65 peptide–MHC class I complexes are molecular assemblies formed when the immunodominant phosphoprotein 65 (pp65) of the human cytomegalovirus (CMV) is processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (2.1.3, 2.2.2). These complexes serve as the primary target for CD8+ cytotoxic T lymphocytes (CTLs), which are essential for the immune control of CMV infection and the prevention of viral reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (2.1.1, 3.2.3). The most extensively characterized complex involves the NLVPMVATV peptide presented by the HLA-A*02:01 allele, a high-frequency variant in the human population (2.1.3, 2.2.2). Beyond infectious disease, CMV pp65 has been identified as a tumor-associated antigen in certain malignancies, including glioblastoma and medulloblastoma, where it is expressed in tumor cells but not in healthy brain tissue (2.2.4, 3.3.1). Therapeutic approaches targeting these complexes include the adoptive transfer of virus-specific T cells (e.g., Posoleucel, ATA230), peptide-based vaccines (e.g., PEP-CMV), and engineered T-cell receptor (TCR)-like antibodies designed to bind the pMHC with high affinity (3.1.1, 3.4.1, 3.5.2). While highly specific, these therapies face challenges such as strict HLA restriction and the ability of CMV to downregulate MHC expression to evade immune detection (2.1.4, 3.5.2).

Other names

CMV pp65 peptide-HLA-A*02:01 complexNLVPMVATV/HLA-A*02:01 complexHCMV pp65 peptide-MHC complexCMV pp65/HLA-A*02:01 complexCytomegalovirus phosphoprotein 65 peptide-MHC class I complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to the targeted lysis of cells presenting the viral antigen.