HLA-A*02:01-presented EBV EBNA1-derived peptide (HLA-A*02:01/EBNA1 peptide)

The HLA-A*02:01-presented EBV EBNA1-derived peptide is a molecular complex formed by the association of a specific peptide fragment from the Epstein-Barr virus nuclear antigen 1 (EBNA1) with the Human Leukocyte Antigen (HLA) A*02:01 molecule (UniProt P03211). EBNA1 is a multifunctional viral protein essential for the replication, segregation, and maintenance of the EBV episome in host cells, and it is uniquely expressed in all EBV-associated malignancies, including Nasopharyngeal Carcinoma, Burkitt lymphoma, and Hodgkin lymphoma (PubMed 25607443). As an intracellular protein, EBNA1 is processed into peptides, such as the FMVFLQTHI epitope, which are then presented on the cell surface by MHC Class I molecules like HLA-A*02:01 for recognition by CD8+ cytotoxic T cells (IEDB). This peptide-MHC complex serves as a highly specific therapeutic target for immunotherapies, including T-cell receptor (TCR) engineered T-cells and TCR-like antibodies, which aim to selectively eliminate EBV-infected or transformed cells (PubMed 30305461). Clinical applications of targeting this complex are particularly relevant in patients with EBV-positive tumors that have failed conventional therapies. However, therapeutic development must address challenges such as the potential for cross-reactivity with self-peptides, as seen in the molecular mimicry between EBNA1 and the glial cell adhesion molecule (GlialCAM) in multiple sclerosis (PubMed 35073561).

Other names

EBNA1/HLA-A*02:01 complexEBV EBNA1 peptide-MHC complexHLA-A*02:01-restricted EBNA1 epitopeFMVFLQTHI/HLA-A*02:01 complex

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity