Cytomegalovirus phosphoprotein 65-derived peptide–Human Leukocyte Antigen class I complex (CMV pp65–HLA-I complex)

The Cytomegalovirus phosphoprotein 65-derived peptide–Human Leukocyte Antigen class I complex (CMV pp65–HLA-I) is a molecular assembly consisting of a processed peptide from the CMV pp65 protein (UL83) bound within the groove of an HLA class I molecule, most commonly HLA-A*02:01 (PubMed: 10449775). This complex is expressed on the surface of cells infected with Human Cytomegalovirus (HCMV) and serves as a primary signal for the host's adaptive immune system, specifically for CD8+ cytotoxic T lymphocytes (CTLs) (UniProt: P06725). The pp65 protein is the most abundant tegument protein and a dominant target of the cellular immune response during both primary infection and reactivation (PubMed: 15507653). In clinical practice, this complex is a major target for immunotherapy, including adoptive transfer of CMV-specific T cells and engineered TCR-T cell therapies, particularly in hematopoietic stem cell transplant (HSCT) recipients who are at high risk for CMV-related complications (PubMed: 28811470). Therapeutic strategies often utilize the highly immunodominant NLVPMVATV peptide to redirect the immune system against infected cells. However, the efficacy of these treatments is restricted by the patient's HLA type and the potential for viral immune evasion through the downregulation of HLA molecules (PubMed: 11752711).

Other names

CMV pp65 peptide-MHC complexpp65-HLA-A*02:01 complexNLVPMVATV-HLA-A*02:01 complexCMV UL83 peptide-HLA complexCMV pp65-MHC-I

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) or TCR-like molecules, leading to the activation of cytotoxic mechanisms and lysis of the target cell.