Cytomegalovirus phosphoprotein 65-derived peptides presented on Major Histocompatibility Complex (CMV pp65-MHC)

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the most abundant tegument protein of Human Cytomegalovirus (HCMV) and serves as a dominant target for the host's cellular immune response (UniProt P06725). During infection, pp65 is processed into short peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily MHC Class I (e.g., HLA-A*02:01), where they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (PubMed: 15605018). This recognition is crucial for the control of CMV replication and the maintenance of viral latency in healthy individuals. In clinical settings, these peptide-MHC complexes are targeted to treat CMV reactivation in immunocompromised patients, such as hematopoietic stem cell transplant recipients, using adoptive T-cell therapies like Viralym-M or vaccines like Triplex (ClinicalTrials.gov: NCT03464877, NCT02396134). Additionally, because pp65 expression has been reported in certain malignancies like glioblastoma, these complexes are being investigated as targets for cancer immunotherapy (PubMed: 28242717). The therapeutic approach typically involves either the infusion of ex vivo expanded CMV-specific T cells or the administration of vaccines designed to elicit a robust T-cell response against cells presenting these specific viral peptides.

Other names

pp65-MHC complexUL83-derived peptides on HLACMV pp65 antigenHuman cytomegalovirus phosphoprotein 65HCMV pp65-MHC

The primary mechanism of action involves the recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ or CD4+ T cells, leading to the activation of the T cells and subsequent lysis of the target cell or the release of antiviral cytokines. Vaccines targeting this complex aim to expand the endogenous pool of these specific T cells, while adoptive T-cell therapies provide an exogenous source of pre-activated cells to control viral replication or tumor growth.