Epstein-Barr virus latent membrane protein 2A peptide–major histocompatibility complex class I complex (LMP2A-pMHC)

The Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) peptide–major histocompatibility complex (MHC) class I complex is a critical target for immunotherapy in EBV-associated malignancies, such as Hodgkin lymphoma and nasopharyngeal carcinoma (UniProt: P13285). LMP2A is a viral protein expressed during EBV latency that mimics B-cell receptor (BCR) signaling, providing survival signals to infected cells and preventing viral reactivation (PMID: 25605874). Because LMP2A is an intracellular membrane protein, it is processed by the cellular proteasome into short peptides, which are then transported and presented on the cell surface by MHC class I molecules, most commonly HLA-A*02:01 (PMID: 30249036). This pMHC complex acts as a specific marker for EBV-infected cells, allowing them to be targeted by T-cell receptor (TCR)-engineered T cells or TCR-like antibodies that recognize the peptide-MHC configuration with high specificity. Therapeutic development focusing on this complex aims to overcome the limitations of targeting surface antigens by accessing the intracellular viral proteome. However, challenges include the potential for tumor cells to downregulate MHC expression to escape immune detection and the risk of off-target toxicity if the targeted viral peptide shares structural similarity with human self-peptides (PMID: 31434705).

Other names

EBV LMP2A-HLA complexLMP2A-MHC-I complexHLA-A*02:01/LMP2A peptide complexLMP2A-pMHCCLGGLLTMV-HLA-A*02:01 complex

Targeted cell lysis via T-cell receptor (TCR) or TCR-like antibody recognition of the viral peptide presented by MHC class I molecules.