Epstein-Barr virus (EBV)-encoded membrane protein LMP1 from a nasopharyngeal carcinoma is non-immunogenic in a murine model system, in contrast to a B cell-derived homologue

Abstract

Epstein-Barr virus (EBV)-encoded LMP1 gene derived from a nude mouse passaged nasopharyngeal carcinoma (NPC) of Chinese origin (C-LMP1) and its B cell (B95-8 prototype)-derived counterpart (B-LMP1) were compared for their ability to induce tumour rejection in a mouse mammary adenocarcinoma system. Each of the two LMP1 genes was introduced individually by retroviral vectors into a non-immunogenic mammary carcinoma line, S6C, that originated in an ACA (H-2f) mouse. Syngeneic ACA mice were immunised for 3 consecutive weeks with irradiated B- or C-LMP1 expressors or control cells. The immunised and control mice were then challenged with graded numbers of viable cells from the corresponding cell line. Only the B-LMP1 expressing cells were highly immunogenic. Up to 10(5) cells were rejected in pre-immunised mice, whereas at least 10(2) cells grew in non-immunised controls. No rejection response was detected against the C-LMP1 expressing cells which grew equally well in control and immunised mice, with a minimum inoculum of 10(2) cells in the majority of the clones. In a previous study, we found numerous sequence differences between B- and C-LMP1. The question of whether any of these differences is related to the non-immunogenicity of C-LMP1 needs further investigation. Meanwhile, our findings raise the possibility that the NPC cells may escape host rejection by the development of a non-immunogenic LMP1 variant under the impact of immunoselection.