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*
Department of Microbiology and Immunology, The Medical School, Newcastle, United Kingdom;
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale U277, Institut Pasteur, Paris, France;
Transplantation Biology Unit, Medical Research Council Clinical Sciences Centre, London, United Kingdom;
§
Department of Neurology, The Medical School, Newcastle, United Kingdom; and
¶
Institute for Cancer Studies, The Medical School, Sheffield, United Kingdom
Fetal mouse 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 fetal 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 fetal 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. Fetal 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.
This article has been cited by other articles:
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  F. Gays, J. G. Aust, D. M. Reid, J. Falconer, N. Toyama-Sorimachi, P. R. Taylor, and C. G. Brooks Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells J. Immunol., November 1, 2006; 177(9): 5840 - 5851. [Abstract] [Full Text] [PDF]
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 S. Nguyen, N. Dhedin, J.-P. Vernant, M. Kuentz, A. A. Jijakli, N. Rouas-Freiss, E. D. Carosella, A. Boudifa, P. Debre, and V. Vieillard NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect Blood, May 15, 2005; 105(10): 4135 - 4142. [Abstract] [Full Text] [PDF]
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B. T. Wilhelm, J.-R. Landry, F. Takei, and D. L. Mager Transcriptional Control of Murine CD94 Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types J. Immunol., October 15, 2003; 171(8): 4219 - 4226. [Abstract] [Full Text] [PDF]
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 J. A. Toomey, F. Gays, D. Foster, and C. G. Brooks Cytokine requirements for the growth and development of mouse NK cells in vitro J. Leukoc. Biol., August 1, 2003; 74(2): 233 - 242. [Abstract] [Full Text] [PDF]
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F. Stevenaert, K. Van Beneden, A. De Creus, V. Debacker, J. Plum, and G. Leclercq Ly49E expression points toward overlapping, but distinct, natural killer (NK) cell differentiation kinetics and potential of fetal versus adult lymphoid progenitors J. Leukoc. Biol., June 1, 2003; 73(6): 731 - 738. [Abstract] [Full Text] [PDF]
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R. H. Lian, M. Maeda, S. Lohwasser, M. Delcommenne, T. Nakano, R. E. Vance, D. H. Raulet, and F. Takei Orderly and Nonstochastic Acquisition of CD94/NKG2 Receptors by Developing NK Cells Derived from Embryonic Stem Cells In Vitro J. Immunol., May 15, 2002; 168(10): 4980 - 4987. [Abstract] [Full Text] [PDF]
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K. Van Beneden, A. De Creus, F. Stevenaert, V. Debacker, J. Plum, and G. Leclercq Expression of Inhibitory Receptors Ly49E and CD94/NKG2 on Fetal Thymic and Adult Epidermal TCR V{gamma}3 Lymphocytes J. Immunol., April 1, 2002; 168(7): 3295 - 3302. [Abstract] [Full Text] [PDF]
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K. Van Beneden, F. Stevenaert, A. De Creus, V. Debacker, J. De Boever, J. Plum, and G. Leclercq Expression of Ly49E and CD94/NKG2 on Fetal and Adult NK Cells J. Immunol., April 1, 2001; 166(7): 4302 - 4311. [Abstract] [Full Text] [PDF]
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N. Toyama-Sorimachi, Y. Taguchi, H. Yagita, F. Kitamura, A. Kawasaki, S. Koyasu, and H. Karasuyama Mouse CD94 Participates in Qa-1-Mediated Self Recognition by NK Cells and Delivers Inhibitory Signals Independent of Ly-49 J. Immunol., March 15, 2001; 166(6): 3771 - 3779. [Abstract] [Full Text] [PDF]
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F. Gays, K. P. Fraser, J. A. Toomey, A. G. Diamond, M. M. Millrain, P. J. Dyson, and C. G. Brooks Functional Analysis of the Molecular Factors Controlling Qa1-Mediated Protection of Target Cells from NK Lysis J. Immunol., February 1, 2001; 166(3): 1601 - 1610. [Abstract] [Full Text] [PDF]
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S. Hui Jia, Z. Kurepa, A. Bai, and J. Forman Comparative Ability of Qdm/Qa-1b, Kb, and Db to Protect Class Ilow Cells from NK-Mediated Lysis In Vivo J. Immunol., December 1, 2000; 165(11): 6142 - 6147. [Abstract] [Full Text] [PDF]
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F. Gays, M. Unnikrishnan, S. Shrestha, K. P. Fraser, A. R. Brown, C. M. G. Tristram, Z. M. A. Chrzanowska-Lightowlers, and C. G. Brooks The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin J. Immunol., May 15, 2000; 164(10): 5094 - 5102. [Abstract] [Full Text] [PDF]
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