Cytomegalovirus phosphoprotein 65 peptide–Human leukocyte antigen complex (CMV pp65–HLA complex)

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the primary tegument protein of Human Cytomegalovirus (HCMV) and serves as the dominant target for the host's cellular immune response (UniProt P06725). During infection, pp65 is processed into peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) Class I and Class II molecules (PubMed: 8623477). These peptide-HLA complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T-lymphocytes, triggering an immune response to eliminate infected cells (PubMed: 15507525). In clinical settings, these complexes are the primary targets for adoptive T-cell therapies, such as Posoleucel, and vaccines like Triplex, which aim to restore CMV-specific immunity in immunocompromised transplant recipients (ClinicalTrials.gov: NCT04355364). Monitoring the frequency of T-cells specific to these complexes, often using MHC tetramers or ELISPOT assays, is a critical biomarker for predicting CMV reactivation and guiding therapeutic intervention (PubMed: 11705923). The therapeutic challenge lies in the high polymorphism of HLA alleles, requiring either patient-specific matching or the development of multi-HLA-restricted products.

Other names

pp65-MHC complexUL83 peptide-HLA complexCMV pp65-HLA-A*02:01CMV pp65-HLA-B*07:02pp65-HLA class I/II complex

Recognition by antigen-specific T-cell receptors (TCRs) on CD8+ or CD4+ T-cells, leading to the lysis of CMV-infected cells and the release of antiviral cytokines.