EBV LMP2A-specific T Cell Immune Responses Elicited by Dendritic Cells Loaded with LMP2A Protein

Abstract

Type II Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin's lymphomas consistently express latent membrane 2A (LMP2A) proteins, which have been suggested to be an ideal target for immunotherapy. In previous studies we have demonstrated that using LMP2A protein loaded dendritic cells, the most powerful antigen processing cells in the body can elicit specific and robust anti-tumor cellular immune response in vitro. In this paper, we further investigated the T cell profile of the anti-tumor immune response. We found that LMP2A specific CD4⁺ and CD8⁺ T cells could be stimulated by LMP2A protein loaded dendritic cells (DCs). The Th1 type immune response is dominant in the immune response mediated by LMP2A specific CD4⁺ T cells. The CD8⁺ cytotoxic T cells can lyse LMP2A bearing cells effectively and specifically. The CD8⁺ cytotoxic T cells can also secrete high level of intracellular IFN-γ, which indicates these cells are EBV-LMP2A specific cytotoxic T cells. Altogether, our studies proved that LMP2A protein loaded DCs can elicit anti-tumor cellular immune responses efficiently. This study provides a rationale for the DC-based immunotherapy against EBV-LMP2A expressing malignancies.