The Journal of Experimental Medicine
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Published online 18 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1341/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1341-1354

Original Article

Nonstochastic Coexpression of Activation Receptors on Murine Natural Killer Cells

Hamish R.C. Smitha, Hubert H. Chuanga, Lawrence L. Wanga, Margarita Salcedob, Jonathan W. Heusela, and Wayne M. Yokoyamaa
a Immunology Program and the Rheumatology Division, Department of Medicine and the Department of Pathology, the Center for Arthritis and Related Diseases, and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110
b Unite de Biologie Moleculaire du Gene, Institut National de la Santé e de la Recherche Médicale, U277, Institut Pasteur, 75015 Paris, France

Correspondence to: Wayne M. Yokoyama, Washington University School of Medicine, 660 South Euclid Ave., Box 8045, St. Louis, MO 63110. Tel:314-362-9075 Fax:314-362-9257 E-mail:yokoyama{at}imgate.wustl.edu.

Murine natural killer cells (NK) express lectin-like activation and inhibitory receptors, including the CD94/NKG2 family of receptors that bind Qa-1, and the Ly-49 family that recognizes major histocompatibility complex class I molecules. Here, we demonstrate that cross-linking of NK cells with a new specific anti–Ly-49H mAb induced NK cell cytotoxicity and cytokine production. Ly-49H is expressed on a subset of NK cells and can be coexpressed with Ly-49 inhibitory receptors. However, unlike Ly-49 inhibitory receptors, Ly-49H is not detectable on naive splenic CD3+ T cells, indicating that Ly-49H may be an NK cell–specific activation receptor. In further contrast to the stochastically expressed Ly-49 inhibitory receptors, Ly-49H is preferentially expressed with the Ly-49D activation receptor, and expression of both Ly-49H and Ly-49D is augmented on NK cells that lack receptors for Qa-1 tetramers. On developing splenic NK1.1+ cells, Ly-49D and Ly-49H are expressed later than the inhibitory receptors. These results directly demonstrate that Ly-49H activates primary NK cells, and suggest that expression of Ly-49 activation receptors by NK cells may be specifically regulated on NK cell subsets. The simultaneous expression of multiple activation receptors by individual NK cells contrasts with that of T cell antigen receptors and is relevant to the role of NK cells in innate immunity.

Key Words: 3D10, cytotoxicity, Ly-49H, subset, Ly-49D


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