Target intelligence / Profile preview

Epstein-Barr virus-derived peptide–Human Leukocyte Antigen class I complex (EBV-pHLA-I) (EBV-pHLA-I)

Target
EBV-pHLA-I
Molecular classification
Antigen-MHC class I complex, Protein complex, Major Histocompatibility Complex (MHC)
01

Overview

Epstein-Barr virus (EBV)-derived peptide–HLA class I complexes are molecular assemblies on the surface of infected or transformed cells where viral protein fragments are presented by Human Leukocyte Antigen (HLA) class I molecules [UniProt, PubMed: 21454470]. These complexes are essential for the immune system's ability to detect and destroy EBV-infected cells, as they are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes [Nature Reviews Immunology]. In clinical oncology, these complexes serve as highly specific therapeutic targets for EBV-associated malignancies, such as nasopharyngeal carcinoma and post-transplant lymphoproliferative disorder (PTLD) [NIH/NCI, The Lancet Oncology]. Modern immunotherapies, including adoptive T-cell therapies like tabelecleucel and TCR-engineered T cells, leverage these complexes to direct a potent immune response against tumor cells while sparing healthy tissue [EMA, Atara Biotherapeutics]. The effectiveness of these treatments depends on the specific HLA allele of the patient and the stability of the peptide-HLA interaction [Journal of Virology]. Challenges in targeting these complexes include the potential for viral immune escape through the downregulation of HLA expression and the risk of cross-reactivity with similar self-peptides [Nature Reviews Microbiology, PubMed: 30552149].

Other names
EBV peptide-MHC class I complexEBV pMHC-IEpstein-Barr virus antigen-HLA complexEBV-specific peptide-HLA complexEBV-derived epitope-HLA class I complex
02

Mechanism of action

Recognition of the viral peptide-HLA complex by specific T-cell receptors (TCRs) on CD8+ T cells, triggering the release of perforins and granzymes to induce apoptosis in the target cell [Nature Reviews Immunology, PubMed: 21454470].

03

Biological functions

Antigen presentationT-cell activationImmune surveillanceCytotoxic T-cell recognition
04

Disease associations

InfectionCancerPost-transplant lymphoproliferative disorder (PTLD)Nasopharyngeal carcinomaBurkitt lymphomaHodgkin lymphomaMultiple sclerosis
05

Safety considerations

Cytokine release syndrome (CRS)Graft-versus-host disease (GvHD)Off-target cross-reactivity with self-peptidesHLA downregulation-mediated immune escape [Nature Reviews Microbiology, PubMed: 30552149]
06

Interacting drugs

Tabelecleucel

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeEBV DNA viral loadLMP1/LMP2 expressionEBNA1 expression [The Lancet Oncology, PubMed: 3652149]

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