¹Toomey, J.A., ²Salcedo, M., ³Cotterill, L.A.,  ³Millrain, M.M., ⁴Chrzanowska-Lightowlers, Z, ⁵Lawry, J., ¹Fraser, K.P., ¹Gays, F., ¹Robinson, J.H., ¹Shrestha, S.,  ³Dyson, P.J., and ¹Brooks, C.G.
¹Department of Microbiology and Immunology, The Medical School, Newcastle, NE2 4HH, U.K.; ²Unite de Biologie Moleculaire du Gene, INSERM U277, Institut Pasteur, F-75015 Paris, France;  ³Transplantation Biology Unit, MRC Clinical Sciences Centre, London, W12 0NN, U.K.; ⁴Department of Neurology, The Medical School, Newcastle, NE2 4HH, U.K.; and ⁵Institute for Cancer Studies, The Medical School, Sheffield, S10 2RX, U.K..

J. Immunol. 163,  3176-3184, 1999.
 

Immature NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family.  NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution. Key Data