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* Department of Immunochemistry, Research Institute for Microbial Diseases and
World Premier International Immunology Frontier Research Center, Osaka University, Osaka;
Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Saitama, Japan; and
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143
The paired Ig-like type 2 receptor (PILR), which comprises both inhibitory and activating isoforms, is well conserved among most mammalians. The inhibitory PILR
possesses an ITIM in its cytoplasmic domain, whereas the activating PILRβ does not have an ITIM but transduces activating signals by associating with the ITAM-bearing DAP12 adapter molecule. Both mouse PILR and PILRβ recognize mouse CD99, which is broadly expressed on various cells, including lymphocytes, and is involved in the regulation of immune responses. We herein report that sialylated O-linked sugar chains on CD99 are essential for the recognition by PILR. Mutations of one of two O-glycosylation sites on CD99 significantly reduced recognition of CD99 by the activating PILRβ, whereas recognition by the inhibitory PILR was not affected. In contrast, mutations of both O-glycosylation sites on CD99 completely abrogated the recognition by both PILR and PILRβ. PILR did not recognize CD99 treated with neuraminidase, and CD99 expressed on cells transfected with core 2 β-1,6-N-acetylglucosaminyltransferase was not recognized by PILR. NK cells expressing endogenous activating PILRβ receptors mediated cytotoxicity against cells expressing wild-type CD99 but not cells expressing mutant CD99 that lacked O-glycosylation sites. These findings indicate that sialylated O-linked sugar structures on CD99 play an important role in the recognition of PILR.
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1 This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (to H.A.). L.L.L. is an American Cancer Society Research Professor and is supported by National Institutes of Health Grant AI64520.
2 Current address: Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan
3 Address correspondence and reprint requests to Dr. Hisashi Arase, Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail address: arase{at}biken.osaka-u.ac.jp
4 Abbreviations used in this paper: KIR, killer cell Ig-like receptor; β3Gal-T, β1,3-galactosyltransferase; C2GnT, core 2 β-1,6-N-acetylglucosaminyltransferase; GalNAc, N-acetylgalactosamine; GalNAc--O-benzyl, benzyl-2-acetamido-2-deoxy--D-galactopyranoside; GlcNAc, N-acetylglucosamine; NeuAc, N-acetylneuraminic acid; PILR, paired Ig-like type 2 receptor; ppGaNTases, UDP-N-acetylgalactosamine:polypeptide N-acetyl-galactosaminyltransferases; Siglec, sialic acid-binding Ig-like lectin; ST3GalI, β-galactoside -2,3-sialyltransferase 1.
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  S. Tabata, K. Kuroki, J. Wang, M. Kajikawa, I. Shiratori, D. Kohda, H. Arase, and K. Maenaka Biophysical Characterization of O-Glycosylated CD99 Recognition by Paired Ig-like Type 2 Receptors J. Biol. Chem., April 4, 2008; 283(14): 8893 - 8901. [Abstract] [Full Text] [PDF]
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