Target intelligence / Profile preview

Epstein-Barr nuclear antigen 1 (EBNA1) 573–581 peptide presented by HLA-DPB1*05:01 (EBNA1 573–581/HLA-DP5)

Target
EBNA1 573–581/HLA-DP5
Molecular classification
Peptide-MHC complex, Antigen, HLA Class II complex
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Overview

The EBNA1 573–581 peptide presented by HLA-DP5 is a specific peptide-major histocompatibility complex (pMHC) class II target used in the development of immunotherapies against Epstein-Barr virus (EBV)-associated diseases. EBNA1 is a DNA-binding protein essential for the replication and persistence of the EBV genome and is uniquely expressed in all EBV-related malignancies, including nasopharyngeal carcinoma and various lymphomas. The specific epitope spanning residues 573–581 is processed and presented on the cell surface by the HLA-DPB1*05:01 allele, which is highly prevalent in East Asian populations. This pMHC complex is a primary target for TCR-engineered T-cell therapies (TCR-T) and therapeutic vaccines designed to elicit a robust CD4+ T-cell response. By targeting this complex, clinicians aim to selectively eliminate EBV-infected cells while minimizing damage to healthy, non-infected tissues.

Other names
EBNA1 573-581/HLA-DPB1*05:01 complexEBNA1(573-581) peptide-MHC complexHLA-DP5-restricted EBNA1 epitopeEBNA1 p573-581
02

Mechanism of action

The complex acts as a ligand for specific T-cell receptors (TCRs) on CD4+ T lymphocytes. Binding of a therapeutic TCR to this peptide-MHC complex triggers T-cell activation, cytokine production (such as IFN-gamma), and direct or indirect lysis of EBV-infected cells expressing the EBNA1 protein.

03

Biological functions

Antigen presentationT-cell activationImmune recognitionCD4+ T-cell mediated immunity
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Disease associations

Infection (Epstein-Barr virus)Nasopharyngeal carcinomaHodgkin lymphomaGastric cancerMultiple Sclerosis
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Safety considerations

Off-target toxicity due to potential cross-reactivity with self-peptidesCytokine release syndrome (CRS)HLA restriction (limited to patients carrying the HLA-DPB1*05:01 allele)Immune evasion through HLA downregulation
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Interacting drugs

TCR-engineered T-cell therapies (TCR-T)

1 more in the full profile.

07

Biomarkers

HLA-DPB1*05:01 genotypeEBNA1 protein expressionEBV DNA viral loadEBNA1-specific CD4+ T-cell frequency

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