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- 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- 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- stimulator B cells, but only from C2- individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1+ NK cells that is only observed in C2- individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.