Rescue of the immunotherapeutic potential of a novel T cell epitope in the Epstein–Barr virus latent membrane protein 2

Epstein–Barr virus (EBV)-associated tumors express a limited number of viral antigens but most of them express the latent membrane protein 2 (LMP2). This article describes a peptide derived from LMP2 (residues 396–404, designated LLL) as a potentially useful vaccine. This peptide could at first be defined as an unlikely T cell target as it could not stabilize MHC surface expression in transporter associated with antigen-processing (TAP)-deficient cells. Nevertheless, T lymphocytes reactive to LLL were detected in the peripheral blood of four EBV-seropositive healthy individuals. We have constructed a chimeric molecule in which LLL was fused to the amino-terminal end of the β2 microglobulin (β2m). Autologous dendritic cells constitutively expressing the LLLβ2m molecule were capable of expanding in vitro HLA-A2-restricted anti-LLL T lymphocytes from the peripheral blood of one of the donors. These T lymphocytes exhibited cytolytic activity against target cells expressing the chimeric molecules as well as against EBV-infected lymphoblastoid cells expressing natural LLL–MHC complexes.