Biphasic response of NK cells expressing both activating and inhibitory killer Ig-like receptors

NK cells can co-express inhibitory and activating killer Ig-like receptors (KIR) recognizing the same HLA class I ligand. We present evidence from exp eriments with NK cells expressing both activating (KIR2DS2) and inhibitory (KIR2DL2 and KIR2DL3) receptors that the activating KIR can function withou t apparent interference from the inhibitory KIR. These studies used CD158b mAb that is equally reactive with KIR2DS2, KIR2DL2 and KIR2DL3. First, we s how using plastic-immobilized CD158b mAb that the activating KIR2DS2 is sti mulated, resulting in NK cell division and degranulation. Second, we show u sing soluble CD158b mAb and FcRII(+) P815 cells that high concentrations of CD158b mAb trigger the inhibitory KIR, whereas low concentrations stimulat e the activating KIR2DS2 resulting in NK cell division and cytolysis. These results demonstrate that the activating KIR2DS2 can function on cells co-e xpressing the inhibitory KIR2DL2 and/or KIR2DL3, indicating the potential f or independent function of activating KIR with natural ligand.