Cytomegalovirus phosphoprotein 65 (pp65) antigen presented by Major Histocompatibility Complex (CMV pp65-MHC)

The Cytomegalovirus (CMV) phosphoprotein 65 (pp65), encoded by the UL83 gene, is the primary tegument protein of the human cytomegalovirus and serves as a dominant target for the host cellular immune response [UniProt: P06725, PMID: 15141007]. In the context of immunotherapy, the target is the specific pp65-derived peptide processed and presented on the cell surface by the patient Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 [PMID: 15141007, PMID: 28819144]. This peptide-MHC complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T-lymphocytes, triggering an immune response against CMV-infected cells [PMID: 15141007]. Beyond viral infections, pp65 has been identified as a tumor-associated antigen in certain malignancies, most notably glioblastoma multiforme, where it is expressed in tumor cells but not in healthy brain tissue [PMID: 24711550]. Therapeutic strategies targeting this complex include adoptive T-cell therapies, such as CMV-specific T-cells and TCR-engineered T-cells, as well as peptide or viral-vector vaccines designed to expand the endogenous T-cell population [ClinicalTrials.gov: NCT04354311, PMID: 28819144]. These interventions aim to restore or enhance viral clearance in immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients, and to provide targeted anti-tumor activity in oncology [ClinicalTrials.gov: NCT04354311, PMID: 24711550]. The specificity of this target allows for precision immunotherapy while minimizing damage to non-infected or non-malignant tissues that do not present the viral antigen. Monitoring of pp65-specific T-cell levels and MHC compatibility is crucial for the success of these therapies.

Other names

UL8365 kDa lower matrix phosphoproteinHCMV pp65CMV pp65 peptide-HLA complexHuman cytomegalovirus phosphoprotein 65

Adoptive T-cell transfer providing direct cytotoxic activity against cells presenting pp65 peptides and active immunization to stimulate endogenous pp65-specific T-cell expansion [ClinicalTrials.gov: NCT04354311, PMID: 28819144].