Human leukocyte antigen-peptide complex presenting Epstein-Barr virus latent membrane protein 1 and 2 epitopes (HLA-LMP1/2 pMHC)

The target consists of Human Leukocyte Antigen (HLA) molecules, primarily Class I, presenting specific peptide epitopes derived from the Epstein-Barr Virus (EBV) Latent Membrane Proteins 1 and 2 (LMP1 and LMP2) (Source: Taylor et al., 2015, J Gen Virol). These complexes are expressed on the surface of B cells and epithelial cells during EBV latency programs (Latency II and III), which are associated with various malignancies such as Nasopharyngeal Carcinoma (NPC), Hodgkin Lymphoma, and Post-transplant lymphoproliferative disorder (PTLD) (Source: Young et al., 2016, Nat Rev Cancer). Because LMP1 and LMP2 are intracellular proteins, they are not accessible to standard monoclonal antibodies; however, their presentation as peptide-MHC (pMHC) complexes allows them to be targeted by T-cell receptor (TCR)-based therapies (Source: Heslop et al., 2013, Blood). Therapeutic interventions include adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs), TCR-engineered T cells (TCR-T), and TCR-like antibodies or CAR-Ts designed to recognize the pMHC complex with high affinity (Source: Smith et al., 2017, Cancer Res). This target is highly specific to EBV-infected cells, offering a pathway for precision immunotherapy that exploits the viral origin of the tumor while sparing healthy, non-infected tissues (Source: Atara Biotherapeutics, 2023).

Other names

HLA-LMP1/2 pMHCEBV LMP peptide-MHC complexesLMP1/2-restricted HLA complexesEpstein-Barr virus latent membrane protein epitopesMHC-peptide complexes (LMP1/2)

Recognition of specific viral peptide-HLA complexes by T-cell receptors (TCRs) or TCR-like chimeric antigen receptors (CARs), leading to the activation of cytotoxic signaling pathways (granzyme/perforin) and apoptosis of the target EBV-infected cell (Source: Cho et al., 2018, Clin Cancer Res).