Target intelligence / Profile preview

HLA-A*02:01–Cytomegalovirus pp65 (NLVPMVATV) peptide complex (HLA-A*02:01–pp65) (HLA-A*02:01–pp65)

Target
HLA-A*02:01–pp65
Molecular classification
MHC Class I, Peptide-MHC complex, Antigen-presenting molecule, Receptor
01

Overview

The HLA-A*02:01–CMV pp65 peptide complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule and the immunodominant NLVPMVATV peptide (residues 495-503) derived from the Cytomegalovirus (CMV) phosphoprotein 65 (pp65) (PubMed: 15905523). This complex is expressed on the surface of CMV-infected cells and serves as a primary target for CD8+ cytotoxic T lymphocytes (CTLs) (UniProt: P06725). In clinical settings, it is a major focus for monitoring CMV-specific immune reconstitution in hematopoietic stem cell transplant recipients (PubMed: 21835045). Furthermore, because pp65 is often expressed in glioblastoma and other malignancies, this pMHC complex is targeted by novel immunotherapies, including TCR-engineered T cells and peptide vaccines (PubMed: 25705881). Therapeutic strategies aim to leverage the high affinity of specific TCRs for this complex to induce targeted cell lysis while minimizing off-target effects (PubMed: 30201734). The high prevalence of the HLA-A*02:01 allele and the strong immunogenicity of the pp65 peptide make this complex a cornerstone for developing precision immunotherapies.

Other names
HLA-A*02:01-NLVPMVATVCMV pp65-A2 complexHLA-A2/pp65(495-503)pMHC complex HLA-A*02:01/NLVPMVATVHLA-A*02:01-UL83HLA-A*02:01-NLV
02

Mechanism of action

Binding of T-cell receptors (TCRs) to the pMHC complex to trigger cytotoxic T-lymphocyte activation and targeted cell lysis.

03

Biological functions

Antigen presentationImmune responseT-cell activationCD8+ T-cell recognitionViral latency maintenance
04

Disease associations

InfectionCancerTransplant-related complicationsGlioblastoma
05

Safety considerations

Cross-reactivity with self-peptidesCytokine release syndrome (CRS)Graft-versus-host disease (GvHD)Viral escape mutationsOff-target toxicity
06

Interacting drugs

Triplex vaccine

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 allele positivityCMV seropositivitypp65 antigenemiaNLVPMVATV-specific T-cell frequencypp65 mRNA expression

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