Cytotoxic T lymphocyte responses specific for the Epstein-Barr virus (EBV) were induced in vitro by utilizing autologous EBV-transformed lymphoblastoid cell lines (LCL) as stimulator cells. The primary stimulation of peripheral blood lymphocytes from EBV-seropositive adults with autologous LCL generated effector cells that killed target cells of various cell lines, including EBV genome-positive and -negative lines. However, a competition study with cold target cells revealed that these effector cells comprised at least two immunologically distinct effector cell populations. One was specific for EBV genome-carrying cells, and the other was nonspecific. Repeated stimulations resulted in almost all of the effector cells having a T cell marker as detected by spontaneous rosette formation. The cytotoxic activity of restimulated T cells was augmented against EBV genome-carrying LCL and Raji cells, but was decreased against Molt-4 (EBV-negative T cell line), BJAB (EBV-negative B cell line), and Daudi cells, all of which were originally highly susceptible target cells for EBV-non-specific effector cells. Daudi cells, which lack HLA-A and -B products, were much less susceptible to EBV-specific Tc despite carrying the EBV genome. This suggests that cytotoxicity of EBV-specific Tc requires HLA-A and/or -B, and that killing is not mediated through DRw antigens that are present on Daudi cells.
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Sugamura et al. (1980) studied this question.