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HLA-A*02:01-presented Epstein-Barr virus latent membrane protein 1-derived peptide (HLA-A*02:01/EBV LMP1 peptide)

Target
HLA-A*02:01/EBV LMP1 peptide
Molecular classification
Peptide-MHC complex, Antigen, MHC Class I
01

Overview

The HLA-A*02:01-presented Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)-derived peptide is a peptide-major histocompatibility complex (pMHC) that serves as a critical target for immunotherapy in EBV-associated malignancies. LMP1 is a key oncogenic protein of EBV that mimics CD40 signaling to promote cell survival and proliferation, and it is expressed in several cancers including nasopharyngeal carcinoma and Hodgkin lymphoma (PMID: 31435311). In individuals with the HLA-A*02:01 allele, specific LMP1-derived peptides (such as YLQQNWWTL) are presented on the cell surface, allowing for recognition by the cellular immune system (PMID: 15163936). This complex is a primary target for T-cell receptor (TCR)-engineered T-cell therapies and bispecific T-cell engagers, which aim to direct a potent cytotoxic response against EBV-positive tumor cells (PMID: 25609110). Because the target is a viral antigen, it offers a high degree of tumor specificity compared to traditional chemotherapy. However, challenges in targeting this complex include the potential for off-target cross-reactivity with human self-peptides and the ability of tumors to evade detection by down-regulating HLA expression (PMID: 30249035).

Other names
HLA-A*02:01/LMP1 complexEBV LMP1 peptide-MHC complexLMP1-derived epitopeYLQQNWWTL/HLA-A*02:01YLLEMLWRL/HLA-A*02:01
02

Mechanism of action

Recognition of the peptide-MHC complex by T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte activation and lysis of target cells.

03

Biological functions

Antigen presentationImmune responseT-cell activation
04

Disease associations

Nasopharyngeal carcinomaHodgkin lymphomaNon-Hodgkin lymphomaEpstein-Barr virus infectionNK/T-cell lymphoma
05

Safety considerations

Cross-reactivity with self-peptidesCytokine release syndrome (CRS)HLA down-regulation (immune evasion)
06

Interacting drugs

LMP1-specific T-cell receptor-engineered T-cells

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeLMP1 protein expressionEBV-encoded small RNA (EBER) statusCirculating EBV DNA

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