Human Leukocyte Antigen A*02:01-restricted Cytomegalovirus phosphoprotein 65 (pp65) peptide (HLA-A*02:01/CMV-pp65)

The Human Leukocyte Antigen A*02:01-restricted Cytomegalovirus phosphoprotein 65 (pp65) peptide complex is a specific peptide-major histocompatibility complex (pMHC) that plays a central role in the cellular immune response against Human Cytomegalovirus (CMV). It consists of the immunodominant nonamer peptide NLVPMVATV, derived from the CMV tegument protein pp65 (UL83), presented by the HLA-A*02:01 molecule on the surface of infected cells (PubMed: 10438932). This complex is the primary target for CD8+ cytotoxic T lymphocytes (CTLs), which recognize the pMHC via their T-cell receptors (TCRs) to initiate the destruction of the virus-harboring cell. In clinical settings, particularly for hematopoietic stem cell and solid organ transplant recipients, this complex is a major therapeutic target for adoptive T-cell therapies and vaccines designed to prevent or treat CMV reactivation (ClinicalTrials.gov: NCT02390141). Therapeutic interventions include the infusion of donor-derived or engineered TCR-T cells and the administration of peptide-based vaccines like PepVax (PubMed: 26157015). Monitoring the presence and activity of T cells specific to this HLA-A*02:01/pp65 complex serves as a critical biomarker for assessing protective immunity in at-risk patients. However, challenges remain regarding potential off-target toxicities if engineered TCRs cross-react with similar self-peptides presented by HLA-A*02:01.

Other names

HLA-A*0201–presented CMV pp65 peptideNLVPMVATV-HLA-A*02:01 complexCMV pp65(495-503) epitopepMHC HLA-A*02:01/NLVPMVATVHLA-A2/CMV pp65

The complex acts as a specific ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering immune-mediated lysis of CMV-infected cells.