Stochastic acquisition of Qa1 receptors during the development of fetal NKcells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets

Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecu les yet show a limited ability to distinguish between wild-type and MHC cla ss I-deficient target cells, In this paper we report that during their deve lopment in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical cl ass I molecule Qa1(b) associated with the Qdm peptide, but not for soluble forms of the classical class I molecules K-b and D-b, The acquisition of th ese Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4, All fetal N K clones tested, including those that lack detectable Qa1 receptors, expres s mRNA for CD94 and for both inhibitory and noninhibitory members of the NK G2 family, Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between mild-type and class I-defici ent blasts but, surprisingly, distinguish efficiently between certain wild- type and class I-deficient tumor cells. A variant line that lacks several m embers of the NKG2 family kills both types of tumor cell equally well, sugg esting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution .