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Epstein-Barr virus peptide–Major Histocompatibility Complex (EBV pMHC) (EBV pMHC)

Target
EBV pMHC
Molecular classification
Antigen-MHC complex, Protein complex
01

Overview

Epstein-Barr virus (EBV) peptide–Major Histocompatibility Complex (pMHC) complexes are molecular assemblies on the surface of EBV-infected or EBV-antigen-expressing cells, consisting of viral protein fragments (peptides) bound to human leukocyte antigen (HLA) molecules. These complexes are the primary targets for the adaptive immune system, specifically T-cell receptors (TCRs) on CD8+ cytotoxic T-lymphocytes, which recognize them to initiate the destruction of infected cells (Hislop et al., 2007, Nature Reviews Microbiology). In the context of EBV-associated diseases, such as post-transplant lymphoproliferative disorder (PTLD), nasopharyngeal carcinoma, and various lymphomas, these pMHCs present antigens like EBNA1, LMP1, and LMP2, which are essential for viral latency and oncogenesis (Taylor et al., 2015, Philosophical Transactions of the Royal Society B). Therapeutic interventions, including adoptive T-cell therapies like Tabelecleucel and engineered TCR-T cells, specifically target these pMHC complexes to eliminate malignant or infected cells while sparing healthy tissue (Prockop et al., 2020, JCI). However, the high degree of HLA polymorphism means that these therapies must be matched to the patient's specific HLA type, posing a challenge for universal application (Bollard & Heslop, 2016, Blood). Monitoring EBV DNA load and HLA status serves as critical biomarkers for the clinical management of patients receiving these targeted therapies (Haque et al., 2007, Lancet Oncology).

Other names
EBV pMHCEpstein-Barr virus antigen-MHC complexHLA-restricted EBV antigensEBV-specific peptide-HLA complex
02

Mechanism of action

Recognition of viral peptides presented on HLA molecules by T-cell receptors, leading to cytotoxic T-lymphocyte activation and targeted cell lysis.

03

Biological functions

Antigen presentationImmune responseT-cell activationCell-mediated immunity
04

Disease associations

InfectionCancerPost-transplant lymphoproliferative disorderNasopharyngeal carcinomaBurkitt lymphomaHodgkin lymphomaMultiple sclerosis
05

Safety considerations

Off-target toxicity due to molecular mimicryCytokine release syndromeGraft-versus-host disease in allogeneic settingsHLA restriction limiting patient eligibility
06

Interacting drugs

Tabelecleucel

2 more in the full profile.

07

Biomarkers

EBV DNA viral loadHLA-A*02:01 genotypeLMP1 expressionLMP2 expressionEBNA1 expression

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