Target intelligence / Profile preview

Cytomegalovirus phosphoprotein 65 (pp65) epitopes presented by HLA class I (CMV pp65 HLA-I epitopes)

Target
CMV pp65 HLA-I epitopes
Molecular classification
Viral protein, Antigen, Peptide-MHC complex
01

Overview

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is a major tegument protein of Human Cytomegalovirus (HCMV) and serves as a dominant target for the host's cellular immune response (UniProt P06725). During the viral life cycle, pp65 is processed by the proteasome into short peptide epitopes, typically 8-11 amino acids in length, which are then transported to the endoplasmic reticulum and loaded onto HLA class I molecules. These peptide-HLA complexes are displayed on the cell surface, where they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (PubMed: 10880463). This recognition is a critical component of viral clearance and long-term latency control. In clinical settings, particularly for immunocompromised transplant recipients, these epitopes are utilized as targets for adoptive T-cell therapies and prophylactic vaccines to prevent CMV reactivation and disease (PubMed: 28923900). Because these epitopes are HLA-restricted, therapeutic efficacy is dependent on the match between the patient's HLA alleles and the specific peptides presented, such as the common NLVPMVATV peptide presented by HLA-A*02:01 (IEDB).

Other names
UL83 epitopesCMV pp65 peptidesHLA-restricted CMV pp65 epitopesHuman betaherpesvirus 5 phosphoprotein 65 epitopespp65-derived HLA class I restricted peptides
02

Mechanism of action

Binding of T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes to the peptide-HLA class I complex on the surface of infected cells, leading to T-cell activation, secretion of inflammatory cytokines (e.g., IFN-gamma), and direct lysis of the target cell (PubMed: 15507653, PubMed: 28923900).

03

Biological functions

Immune responseAntigen presentationT-cell activationViral latency maintenance
04

Disease associations

InfectionCytomegalovirus infectionPost-transplant complicationsCongenital CMV infection
05

Safety considerations

Graft-versus-host disease (GvHD) in allogeneic settingsCytokine release syndrome (CRS)HLA restriction limiting patient eligibilityImmune evasion through viral mutations in epitope sequencesPotential for off-target cross-reactivity with self-peptides
06

Interacting drugs

Viralym-M (ALVR106)

4 more in the full profile.

07

Biomarkers

HLA-A*02:01HLA-B*07:02HLA-A*24:02CMV viral load (DNA PCR)pp65-specific T-cell frequency (ELISPOT)MHC-peptide tetramer staining

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