J. Exp. Med., Volume 186, Number 12, December 15, 1997 1957-1963

Association with FcR Is Essential for Activation Signal through NKR-P1 (CD161) in Natural Killer (NK) Cells and NK1.1⁺ T Cells

By Noriko Arase,^* Hisashi Arase,^* Seung Yong Park,^* Hiroshi Ohno,^* Chisei Ra, and Takashi Saito^*

From the ^* Division of Molecular Genetics, Center for Biological Science, Chiba University School of Medicine, Chiba 260, Japan; and the  Department of Immunology, Juntendo University School of Medicine, Tokyo 113, Japan

Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-linking of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN- production. However, molecular mechanism of NK cell activation via NKR-P1 is not well elucidated. In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcR chain which is an essential component of Fc receptors for IgG and IgE. The association between FcR and NKR-P1 is independent of Fc receptor complexes. Furthermore, NK cells from FcR-deficient mice did not show cytotoxicity or IFN- production upon NKR-P1 cross-linking. Similarly, NK1.1⁺ T cells from FcR-deficient mice did not produce IFN- upon NKR-P1 crosslinking. These findings demonstrate that the FcR chain plays an important role in activation of NK cells via the NKR-P1 molecule.

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