Epstein-Barr virus latent membrane protein 2A peptide–Human leukocyte antigen complex (LMP2A-HLA complex)

The Epstein-Barr virus latent membrane protein 2A peptide–Human leukocyte antigen complex is a therapeutic target consisting of viral peptides presented by MHC class I molecules on the surface of EBV-infected cells (PMID: 10933728). LMP2A is a key protein that maintains EBV latency and promotes oncogenesis by mimicking B-cell receptor signaling, making it a consistent marker in EBV-associated malignancies (PMID: 29434374). This complex is specifically targeted by adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T), which are designed to recognize the peptide-HLA configuration with high affinity (NCT04509596). It is particularly relevant in the treatment of nasopharyngeal carcinoma, EBV-positive gastric cancer, and Hodgkin lymphoma where LMP2A is expressed (PMID: 31534003). Drugs like Tabelecleucel utilize T-cell recognition of such EBV antigens to treat post-transplant lymphoproliferative disorders (PMID: 32814729). However, therapeutic challenges include the potential for HLA downregulation by tumor cells and the risk of off-target cross-reactivity with similar human self-peptides (PMID: 25635008).

Other names

EBV LMP2A-MHC complexLMP2A-HLA-A*02:01 complexLatent membrane protein 2A-HLA complexLMP2A pMHC

Recognition of the viral peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to targeted cytotoxic T-lymphocyte (CTL) activation and apoptosis of EBV-infected cells.