Target intelligence / Profile preview

Cytomegalovirus phosphoprotein 65 (pp65) antigenic epitopes presented on HLA class I (CMV pp65/HLA-I)

Target
CMV pp65/HLA-I
Molecular classification
Antigenic peptide-MHC complex, Viral protein fragment, Other
01

Overview

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is a major tegument protein of Human Cytomegalovirus (HCMV) and serves as the primary immunodominant target for the host's cytotoxic T-lymphocyte (CTL) response (UniProt: P06725) [1]. During infection, pp65 is processed into short peptide fragments, or epitopes, which are then loaded onto HLA Class I molecules and presented on the surface of infected cells (PubMed: 15507644) [2]. This presentation allows CD8+ T cells to recognize and eliminate CMV-infected cells, playing a critical role in maintaining viral latency and preventing symptomatic disease (PubMed: 25605961) [3]. In clinical settings, particularly among hematopoietic stem cell and solid organ transplant recipients, the failure of this immune surveillance leads to life-threatening CMV reactivation (PubMed: 28928955) [4]. Consequently, pp65/HLA-I complexes are targeted by various immunotherapeutic approaches, including adoptive cell therapies using ex vivo expanded CMV-specific T cells and peptide-based vaccines designed to bolster the endogenous immune response (ClinicalTrials.gov: NCT02133313) [5]. These therapies aim to restore the cellular immune control that is lost during immunosuppression, providing a targeted alternative to traditional antiviral drugs (PubMed: 30123502) [6].

Other names
HCMV pp65UL83CMV pp65 peptide-MHC complexpp65-derived HLA-restricted epitopesHuman cytomegalovirus phosphoprotein 65
02

Mechanism of action

Recognition of the peptide-HLA complex by CD8+ T-cell receptors (TCRs) to induce cytotoxic lysis of infected cells and pro-inflammatory cytokine production.

03

Biological functions

Immune responseAntigen presentationT-cell activationViral latency regulationOther
04

Disease associations

InfectionPost-transplant CMV reactivationCongenital CMV infectionOther
05

Safety considerations

Graft-versus-host disease (GvHD) in allogeneic settingsCytokine release syndrome (CRS)Immune evasion via viral downregulation of HLA Class IOff-target toxicity due to TCR cross-reactivity
06

Interacting drugs

CMV-specific T-lymphocytes (CMV-VST)

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypepp65-specific CD8+ T-cell frequency (Tetramer/ELISPOT)CMV viral load (DNAemia)

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