J. Exp. Med., Volume 189, Number 3, February 1, 1999 493-500

Mouse Ly-49D Recognizes H-2D^d and Activates Natural Killer Cell Cytotoxicity

By Mary C. Nakamura,^* Paul A. Linnemeyer,^* Eréne C. Niemi,^* Llewellyn H. Mason, John R. Ortaldo, James C. Ryan,^* and William E. Seaman^*§

From the ^* Department of Medicine, University of California San Francisco, San Francisco, California 94143, and the Veterans Administration Medical Center, San Francisco, California 94121; the  Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702; and the ^§ Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California 94143

Although activation of natural killer (NK) cytotoxicity is generally inhibited by target major histocompatibility complex (MHC) class I expression, subtle features of NK allorecognition suggest that NK cells possess receptors that are activated by target MHC I. The mouse Ly-49D receptor has been shown to activate NK cytotoxicity, although recognition of MHC class I has not been demonstrated previously. To define Ly-49D-ligand interactions, we transfected the mouse Ly-49D receptor into the rat NK line, RNK-16 (RNK.mLy-49D). As expected, anti- Ly-49D monoclonal antibody 12A8 specifically stimulated redirected lysis of the Fc receptor- bearing rat target YB2/0 by RNK.mLy-49D transfectants. RNK.mLy-49D effectors were tested against YB2/0 targets transfected with the mouse MHC I alleles H-2D^d, D^b, K^k, or K^b. RNK.mLy-49D cells lysed YB2/0.D^d targets more efficiently than untransfected YB2/0 or YB2/0 transfected with D^b, K^k, or K^b. This augmented lysis of H-2D^d targets was specifically inhibited by F(ab')₂ anti-Ly-49D (12A8) and F(ab')₂ anti-H-2D^d (34-5-8S). RNK.mLy-49D effectors were also able to specifically lyse Concanavalin A blasts isolated from H-2^d mice (BALB/c, B10.D2, and DBA/2) but not from H-2^b or H-2^k mice. These experiments show that the activating receptor Ly-49D specifically interacts with the MHC I antigen, H-2D^d, demonstrating the existence of alloactivating receptors on murine NK cells.

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