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International Immunology, Vol. 16, No. 4, pp. 533-538, April 2004
© 2004 Japanese Society for Immunology

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Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112)

Satoko Tahara-Hanaoka1,3, Kazuko Shibuya1,2, Yuko Onoda1, Hua Zhang3, Satoshi Yamazaki1,3, Akitomo Miyamoto1, Shin-ichiro Honda1,3, Lewis L. Lanier4 and Akira Shibuya1,2,3

1 Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, RIKEN, Tsukuba, Ibaraki 305-0074, Japan 2 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan 3 PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan 4 Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143-0414, USA

Correspondence to: A. Shibuya, Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-3585, Japan. E-mail: ashibuya{at}md.tsukuba.ac.jp
Transmitting editor: K. Takatsu

CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226. Ectopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more susceptible to IL-2-activated T and NK cell-mediated cytotoxicity, and killing was specifically inhibited by anti-CD226 mAb, demonstrating functional interactions of CD226 with CD155 and CD112. Although the binding affinities between soluble CD226 and CD155 or CD112 were comparable, the homophilic interaction of cell-surface CD112 may adversely affect CD226 binding to CD112. We also demonstrate that ligation of CD226 and LFA-1 with their respective ligands cooperates in triggering cytotoxicity and cytokine secretion by T and NK cells.

Keywords: adhesion molecule, cytotoxic T lymphocyte, cytotoxicity, NK cell, tumor immunity


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