Cytolytic T lymphocytes from HLA-B8+ donors frequently recognize the Hodgkin's lymphoma associated latent membrane protein 2 of Epstein Barr virus

The human γ-herpesvirus Epstein Barr virus (EBV) establishes a life-long, mostly asymptomatic infection in more than 90% of human adults. In immune competent hosts, it persists in latently infected B cells. EBV reservoirs under immune control are located in the peripheral blood and secondary lymphoid organs like the tonsils. Virus infected na？ve B cells in tonsils of healthy EBV carriers express all latent antigens, the six nuclear antigens (EBNA1, 2, 3A, 3B, 3C and LP) and the two membrane proteins (LMP1 and 2)[1]. This expression pattern can also be found after transformation of B cells in immunosuppressed hosts or in vitro generated lymphoblastoid cell lines (LCL)[2]. The subset of virus carrying centroblasts and centrocytes in donors that have established immune control of EBV only express EBNA1, LMP1 and LMP2[1,3]. This expression pattern is also found in most spontaneously arising EBV associated malignancies, like Hodgkin's disease and nasopharyngeal carcinoma[4]. In peripheral blood, EBV can be found in memory B cells expressing none of the latent EBV antigens[5] or EBNA1 during homeostatic proliferation[6]. Thus, healthy EBV carriers already harbor EBV infected B cells with transforming viral antigen expression patterns similar to EBV associated malignancies.EBV transformed B cells are controlled by T cell immunity in healthy EBV carriers[7]. This becomes apparent in patients with T cell compromising co-infection with the human immunodeficiency virus (HIV), genetic lesions like X-linked lymphoproliferative disease (XLP) and immunosuppressive treatment after allograft transplantation. In all these instances EBV associated lymphomas occur at increased frequencies with especially in XLP patients often fatal outcome[4,8-10]. Some of these can be treated by adoptive transfer of in vitro expanded T cell lines[11], suggesting that T cells form a crucial component of EBV specific immune control.Some of these lines are dominated by CD8+ T cells specific for EBNA3 pro