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

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

Overview

Cytomegalovirus phosphoprotein 65 (pp65), encoded by the UL83 gene, is the primary tegument protein of Human Cytomegalovirus (HCMV) and serves as the immunodominant target for the host's CD8+ cytotoxic T-lymphocyte (CTL) response [1, 2]. During infection, pp65 is processed into short peptide epitopes that are presented on the cell surface by matched HLA class I molecules [3]. These HLA-peptide complexes are recognized by specific T-cell receptors (TCRs), which triggers an effector response involving the release of cytotoxins like granzymes and perforins to eliminate the infected cell. While the NLVPMVATV epitope (restricted by HLA-A*02:01) is the most frequently targeted in research, a wide variety of other epitopes restricted by diverse HLA-A, -B, and -C alleles are essential for comprehensive immune protection across different populations [3, 4]. In clinical practice, these epitopes are utilized as targets for adoptive T-cell therapies and vaccines, particularly to prevent or treat CMV reactivation in immunocompromised patients such as hematopoietic stem cell transplant recipients [5]. Monitoring the frequency and functionality of T cells specific to these epitopes via assays like ELISPOT or MHC multimer staining provides critical biomarkers for assessing immune reconstitution and therapeutic efficacy [4]. Citations: [1] UniProt P06725; [2] Wills et al., 1996 (J. Virol); [3] Sylwester et al., 2005 (J. Exp. Med.); [4] Gratama et al., 2001 (Blood); [5] ClinicalTrials.gov (NCT02313857).

Other names
UL83 epitopesCMV pp65 peptidesHLA-restricted CMV antigenspp65-derived MHC class I ligandsHuman cytomegalovirus phosphoprotein 65 epitopes
02

Mechanism of action

Recognition of the HLA-peptide complex by CD8+ T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) activation, secretion of pro-inflammatory cytokines (IFN-gamma, TNF-alpha), and direct lysis of CMV-infected cells.

03

Biological functions

Immune responseT-cell activationAntigen presentationViral protein processingImmune surveillance
04

Disease associations

Cytomegalovirus infectionPost-transplant CMV reactivationCongenital CMV infectionImmunodeficiency-related CMV disease
05

Safety considerations

Graft-versus-host disease (GvHD) in allogeneic T-cell transferImmune escape through viral downregulation of HLA moleculesOff-target TCR cross-reactivity with self-peptidesCytokine release syndrome (rare)
06

Interacting drugs

CMV-specific T-lymphocytes (e.g., Viralym-M)

4 more in the full profile.

07

Biomarkers

HLA-A/B/C genotypeCMV serostatuspp65-specific T-cell frequency (ELISPOT)MHC tetramer/multimer stainingIntracellular cytokine staining (ICS)

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