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Murine CD160, Ig-Like Receptor on NK Cells and NKT Cells, Recognizes Classical and Nonclassical MHC Class I and Regulates NK Cell Activation¹

Motoi Maeda^2,*, Carmine Carpenito^3,*, Ryan C. Russell^4,*, Jyoti Dasanjh^*, Linnea L. Veinotte^*, Hideaki Ohta^5,*, Takashi Yamamura, Rusung Tan and Fumio Takei^6,*,

^* Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Immunology, National Institute of Neuroscience, Tokyo, Japan; and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Human and mouse NK cells use different families of receptors to recognize MHC class I (MHC I) on target cells. Although human NK cells express both Ig-like receptors and lectin-like receptors specific for MHC I, all the MHC I-specific receptors identified on mouse NK cells to date are lectin-like receptors, and no Ig-like receptors recognizing MHC I have been identified on mouse NK cells. In this study we report the first MHC I-specific Ig-like receptor on mouse NK cells, namely, murine CD160 (mCD160). The expression of mCD160 is restricted to a subset of NK cells, NK1.1⁺ T cells, and activated CD8⁺ T cells. The mCD160-Ig fusion protein binds to rat cell lines transfected with classical and nonclassical mouse MHC I, including CD1d. Furthermore, the level of mCD160 on NK1.1⁺ T cells is modulated by MHC I of the host. Overexpression of mCD160 in the mouse NK cell line KY-2 inhibits IFN- production induced by phorbol ester plus ionomycin, whereas it enhances IFN- production induced by NK1.1 cross-linking or incubation with dendritic cells. Cross-linking of mCD160 also inhibits anti-NK1.1-mediated stimulation of KY-2 cells. Anti-mCD160 mAb alone has no effect. Thus, mCD160, the first MHC I-specific Ig-like receptor on mouse NK cells, regulates NK cell activation both positively and negatively, depending on the stimulus.

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