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Cytomegalovirus phosphoprotein 65 and immediate-early protein 1 peptide-HLA class I complexes (CMV pp65/IE-1 pHLA)

Target
CMV pp65/IE-1 pHLA
Molecular classification
Peptide-MHC complex, Viral antigen, HLA class I restricted antigen
01

Overview

Cytomegalovirus (CMV) phosphoprotein 65 (pp65) and immediate-early protein 1 (IE-1) are immunodominant viral antigens that play a critical role in the host immune response (Stern et al., 2019). During infection, these proteins are proteolytically processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules. These peptide-HLA (pHLA) complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate the lysis of the infected cell to control viral spread (Wills et al., 1996). In clinical settings, particularly following hematopoietic stem cell or solid organ transplantation, these pHLA complexes are primary targets for immunotherapies designed to restore CMV-specific immunity. Current therapeutic approaches include the adoptive transfer of donor-derived or off-the-shelf CMV-specific T cells, as well as vaccines like Triplex that encode these antigens to stimulate endogenous T-cell expansion (City of Hope, 2022). Monitoring the presence of these complexes and the corresponding T-cell frequency is essential for managing CMV reactivation and ensuring the safety and efficacy of T-cell-based interventions (AlloVir, 2023).

Other names
CMV pp65/IE-1 antigensCMV pp65/IE-1 HLA-restricted epitopesCMV pp65/IE-1 peptide-MHC complexesUL83/UL123 HLA complexesCMV-specific T-cell targets
02

Mechanism of action

Targeted recognition by T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) mediated apoptosis of CMV-infected cells

03

Biological functions

Antigen presentationImmune responseT-cell activationViral protein processing
04

Disease associations

InfectionCytomegalovirus infectionPost-transplant complications
05

Safety considerations

Graft-versus-host disease (GvHD)Cytokine release syndrome (CRS)Off-target cross-reactivity with self-peptidesImmune escape via HLA downregulation
06

Interacting drugs

Posoleucel (ALVR105)

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeCMV DNAemiapp65 antigenemiaCMV-specific T-cell frequency

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