Epstein-Barr virus-specific T-cell recognition of B-cell transformants expressing different EBNA 2 antigens

Epstein-Barr (EB) virus isolates can be classified as type A or type B depending upon the identity of the virus-encoded nuclear antigen EBNA 2; the EBNA 2A and 2B proteins show limited amino-acid homology and induce largely non-cross-reactive antibody responses in humans. To examine whether EBNA 2 might also be a target for virus-specific cytotoxic T-cell responses (like "intracellular" antigens in other viral systems), normal B cells from non-immune donors of known HLA type were transformed in vitro with virus isolates either of type A (from the B95-8 and IARC-BL74 cell lines) or of type B (from the AG876 and IARC-BL16 cell lines) to provide a suitable panel of target cells. DNA hybridization with type-specific probes and immunoblotting with type-specific antisera confirmed the EBNA 2 type of the resident virus in the various in vitro transformants. These cells were then tested as targets for virus-specific cytotoxic T cells, the latter being prepared from type-A virus-infected donors by in vitro reactivation of memory cells from peripheral blood using autologous type-A virus-transformed cells as stimulators. Such effector cells lysed type-A virus-transformed and type-B virus-transformed target cells equally well, indicating that EBNA 2 (in particular that part of the protein which varies between virus types) seems not to be a dominant antigen for the induction of EB virus-specific cytotoxic responses.