Target intelligence / Profile preview

HLA-B*08:01-presented Epstein-Barr virus BZLF1 peptide-T-cell receptor complex (HLA-B*08:01-BZLF1-TCR)

Target
HLA-B*08:01-BZLF1-TCR
Molecular classification
MHC class I protein complex, T-cell receptor ligand, Antigen-MHC complex, Receptor
01

Overview

The HLA-B*08:01-presented EBV BZLF1 peptide-T-cell receptor (TCR) complex is a molecular assembly essential for the cellular immune response against Epstein-Barr virus (EBV) (Argaet et al., 1994, J Exp Med). The BZLF1 protein, also known as Zta or ZEBRA, is an immediate-early transcription factor that triggers the EBV lytic cycle (Kjer-Nielsen et al., 2003, Immunity). In individuals carrying the HLA-B*08:01 allele, the immunodominant peptide RAKFKQLL (residues 190–197) from BZLF1 is processed and presented on the surface of infected cells (Gras et al., 2009, J Immunol). This peptide-MHC (pMHC) complex is specifically recognized by the TCRs of CD8+ cytotoxic T lymphocytes (CTLs), leading to the release of cytotoxic granules that destroy the EBV-infected cell. This complex is a major focus for immunotherapy, particularly in treating EBV-associated diseases such as post-transplant lymphoproliferative disorder (PTLD) and certain lymphomas (Prock et al., 2023, Front Immunol). Therapeutic strategies include the use of adoptive T-cell therapies, such as tabelecleucel, and the development of TCR-engineered T cells designed to precisely target this pMHC complex (Haque et al., 2007, Blood).

Other names
HLA-B*08:01-RAKFKQLL complexEBV BZLF1 (190-197) HLA-B8 complexBZLF1-specific TCR-pMHC complexHLA-B8-BZLF1 complexEpstein-Barr virus BZLF1 peptide-HLA-B*08:01 complex
02

Mechanism of action

T-cell receptor-mediated recognition of viral peptide-MHC complex leading to cytotoxic cell death

03

Biological functions

Immune responseAntigen presentationT-cell activationCytolysisAdaptive immunity
04

Disease associations

InfectionPost-transplant lymphoproliferative disorderNasopharyngeal carcinomaHodgkin lymphomaMultiple sclerosisBurkitt lymphoma
05

Safety considerations

Cross-reactivity with self-peptidesCytokine release syndromeOff-target toxicityGraft-versus-host disease
06

Interacting drugs

Tabelecleucel

2 more in the full profile.

07

Biomarkers

HLA-B*08:01 allele positivityEBV DNA loadBZLF1-specific CD8+ T-cell frequencyBZLF1 protein expression

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