CO-STIMULATION WITH B7 AND TARGETED SUPERANTIGEN IS REQUIRED FOR MHC CLASS II-INDEPENDENT T-CELL PROLIFERATION BUT NOT CYTOTOXICITY

The superantigen Staphylococcal enterotoxin A (SEA) conjugated to tumo ur-specific monoclonal antibodies (mAb) directs T cells to lyse tumour cells in the absence of major histocompatibility complex (MHC) class II. In contrast, the conjugate bound to MHC class II-negative tumour c ells did not activate resting T cells to proliferate. The SEA-C215 mAb conjugate, when presented on the CA215 antigen-expressing Colo205 cel ls, required either signalling with CD28 mAb or CHO cells expressing t he natural CD28 ligand, B7, to activate the T cells. The CD28/B7 co-st imulatory effect was further enhanced when the B7 and the tumour antig en were present on the same cell, decreasing the superantigen amount r equired for activation with a factor of 10(4). No influence of B7 was seen when the single CA215 or double CA215/B7 transfectants were used as targets for superantigen conjugate-dependent cytotoxicity. This sug gests that the low affinity T-cell receptor (TcR) interaction of super antigen in the absence of MHC class II antigens is sufficient for indu ction of cytotoxicity but requires additional CD28/B7 signalling to re sult in proliferation of resting T cells.