GENE ACTIVATING AND PROAPOPTOTIC POTENTIAL ARE INDEPENDENT PROPERTIESOF DIFFERENT CD4 EPITOPES

CD4 engagement triggers an early signaling cascade which initiates lat e events such as transcription factor activation. The outcome of CD4 e ngagement is T-cell commitment to alternative, dramatically different fates, such as activation and apoptosis. We have tested a panel of ant i-CD4, mAbs specific for different CD4 epitopes, as well as HIV-1 gp12 0, for the capacity to activate crucial early events such as enhanceme nt of p56lck kinase activity and She phosphoryation. The same CD4 epit opes were characterized for their capacity both to deliver a gene acti vating signal and to program T-cells to activation dependent death. No correlation could be found between capacity of specific CD4 epitopes to deliver a gene activating signal and capacity to prime T-cells to a poptotis, suggesting that gene activating and proapoptotic potential a re independent functions of CD4 epitopes. Furthermore, while triggerin g of the calcium pathway appears critical in NF-AT activation, optimal p561ck activation and She phosphorylation might be required for initi ation of the apoptotic pathway. (C) 1997 Elsevier Science Ltd.