Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions

Abstract : NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1 + NK cells are C2-alloreactive only from C2 À individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1 + NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2 À EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1 + NK cells. In the case of KIR2DL1 + /S1 + genotyped individuals, KIR2DS1 + NK-cell frequency was increased after stimulation with C2 + compared with C2 À stimulator B cells, but only from C2 À individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1 + NK cells that is only observed in C2 À individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.