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 tumour-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 cells did not activate resting T cells to proliferate. The SEA-C215 mAb conjugate, when presented on the CA215 antigen-expressing Colo205 cells, required either signalling with CD28 mAb or CHO cells expressing the natural CD28 ligand, B7, to activate the T cells. The CD28/B7 co-stimulatory effect was further enhanced when the B7 and the tumour antigen were present on the same cell, decreasing the superantigen amount required 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 suggests that the low affinity T-cell receptor (TcR) interaction of superantigen in the absence of MHC class II antigens is sufficient for induction of cytotoxicity but requires additional CD28/B7 signalling to result in proliferation of resting T cells.
Lando
P A
PA
Kabi Pharmacia Therapeutics, Lund, Sweden.
Dohlsten
M
M
Hedlund
G
G
Brodin
T
T
Sansom
D
D
Kalland
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D018106:CD28 Antigens; D004768:Enterotoxins; D006681:HLA-D Antigens; D007369:Interferon Inducers; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal