Introduction: the CTL response to Epstein–Barr virus

Epstein–Barr virus (EBV) is a γ-herpesvirus that is carried by more than 90% of adults worldwide as an asymptomatic persistent infection. This virus is the causative agent of infectious mononucleosis, a benign lymphoproliferative disease and is also implicated in the pathogenesis of an increasing number of malignant diseases, including: Burkitt's lymphoma (BL), nasopharyngeal carcinoma and Hodgkin's disease (Miller, 1990). The importance of cellular immunity, and especially of CTLs, in controlling the potentially harmful consequences of EBV infection is underscored by the increased incidence of EBV-driven lymphoproliferations in organ transplant recipients receiving immunosuppressive therapy and in AIDS patients (Thomas, Allday & Crawford, 1991).

The pathogenic potential of EBV is well illustrated by the ease with which the virus can infect resting B lymphocytes in vitro, causing growth-transformation and the establishment of lymphoblastoid cell lines (LCLs) with infinite doubling capacity. This in vitro infection model provided the first clue as to how the virus is controlled in vivo. If circulating lymphocytes from EBV-seropositive donors are infected with EBV in vitro without first removing or inactivating the T lymphocytes, then the initial proliferation of EBV-infected B lymphocytes is followed by a regression at two to three weeks post-infection because of reactivation of EBV-specific memory T lymphocytes that eliminate the virus-infected cells (Rickinson et al, 1981). Activated T cells isolated from such cultures contain CTL populations that are HLA class I-restricted and specific for EBV-encoded antigens.