Human T-cell hybrids with HLA-restricted proliferative response to Epstein-Barr virus-infected B cells

Human T-cell hybrids were constructed from an HGPRT-negative mutant of the acute lymphoblastoid leukaemia cell-line CEM and an uncloned population of T cells from donor SW (SW-T; partner cell) known to have a strong specificity for the autologous Epstein-Barr virus (EBV)-transformed B cell, SWEBV. The resulting hybrids, 1A9, 1D12 and 2C8, were shown not to be cytotoxic to SWEBV, nor did they have natural killer-like (NK) activity. However, when presented with the target SWEBV in a mixed lymphocyte reaction (MLR), all of the hybrids rapidly increased their rate of proliferation by up to a factor of seven. Hybrid 1D12 also produced interleukin-2-like material (IL2) under these conditions. The hybrids did not react with the autologous PHA-blasts (SWPHA), nor with various unrelated targets. When tested against a bank of EBV-transformed B-cell targets, it was observed that the human T-cell hybrids 1A9 and 2C8 responded only to those targets bearing the antigen HLA Bw35. This response could be blocked by treating the target with the monoclonal antibody W6/32, specific for a shared determinant of the HLA-A, -B and -C antigens. Similarly, the human T-cell hybrid 1D12 reacted only against those targets bearing the antigen HLA DrW2, and this activity could be blocked by the monoclonal antibody DA6.231, specific for a common region of the HLA-DR and SB antigens. Thus, human T-cell hybrids can be produced which exhibit HLA-restricted responses to antigenic stimulation.