Target intelligence / Profile preview

Cytomegalovirus phosphoprotein 65 (pp65) antigen-derived peptides presented on MHC class I (CMV pp65-MHC I)

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

Overview

The Cytomegalovirus (CMV) phosphoprotein 65 (pp65), also known as UL83, is a major tegument protein and the most immunodominant target for the host's cellular immune response during CMV infection (UniProt P06725). Peptides derived from pp65 are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, where they are specifically recognized by CD8+ cytotoxic T lymphocytes (PubMed: 15507525). This peptide-MHC complex is a critical target for controlling CMV reactivation in immunocompromised patients, such as those undergoing hematopoietic stem cell or solid organ transplantation (NIH: PMC4110293). Furthermore, CMV pp65 has been identified as a tumor-associated antigen in glioblastoma multiforme, where its expression is restricted to malignant cells, making it a candidate for targeted immunotherapy (PubMed: 24711661). Therapeutic approaches targeting this complex include CMV-specific T-cell therapies, TCR-engineered T cells, and various vaccine platforms like Triplex or peptide-based vaccines (ClinicalTrials.gov: NCT02396134). These therapies work by inducing or providing T cells that recognize the pp65-MHC I complex, leading to the targeted destruction of infected or cancerous cells.

Other names
UL83pp65CMV pp65HLA-restricted CMV pp65 peptideCMV pp65(495-503)NLVPMVATV-MHC complex
02

Mechanism of action

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to CD8+ T-cell activation and cytotoxic lysis of the target cell.

03

Biological functions

Antigen presentationImmune responseViral replicationT-cell activationViral tegument formation
04

Disease associations

InfectionCancerPost-transplant complications
05

Safety considerations

Graft-versus-host disease (GvHD)Cytokine release syndrome (CRS)Off-target toxicity due to TCR cross-reactivityAntigen escape
06

Interacting drugs

Posoleucel (ALVR106)

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 statusCMV serostatuspp65 mRNA expressionpp65 protein expressionCMV DNA viral load

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