Antibodies are capable of directing superantigen-mediated T cell killing of chronic XXXX cells.

@entity1075 @entity42427 @entity5 @entity2936 @entity2225 @entity1072 @entity4621 @entity8624 @entity1778 @entity1583 @entity2071
The bacterial superantigen staphylococcal enterotoxin A (SEA) is a highly potent activator of cytotoxic T cells when presented on MHC class II molecules of target cells. Our earlier studies showed that such SEA-directed T cells efficiently killed chronic @entity8624 ( @entity1072 ) cells. With the ultimate goal to replace the natural specificity of SEA for MHC class II molecules with the specificity of a monoclonal antibody (mAb), we initially made a mutated protein A-SEA (PA-SEAm) fusion protein with > 100-fold reduced binding affinity for MHC class II compared to native SEA. The fusion protein was successfully used to direct T cells to @entity1072 cells coated with different B lineage specific ( @entity1075 , @entity2225 ) or associated ( @entity42427 , @entity2936 ) mAbs. The PA-SEAm protein was 10-100-fold more potent against mAb coated compared to uncoated HLA class II+ @entity1072 cells. No correlation was seen between the amount of mAb bound to the cell surface and sensitivity to lysis. Preactivation of @entity1072 cells by @entity4621 increased their sensitivity, and lysis was dependent on @entity2071 molecules. However, no preactivation of the target cells was needed when a cocktail of two or four mAbs was used. Circulating @entity1778 and spleen cells were equally well killed. We conclude that the natural target specificity of SEA, MHC class II, can be reduced by mutagenesis and novel binding specificity can be introduced by linkage to @entity5 reactive mAbs. Our findings encourage the construction of recombinant SEA mutant fusion proteins for specific T cell therapy of @entity1583 such as @entity1072 .
