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Molecular and Cellular Biology, September 2005, p. 7743-7757, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7743-7757.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD26 Mediates Dissociation of Tollip and IRAK-1 from Caveolin-1 and Induces Upregulation of CD86 on Antigen-Presenting Cells

Kei Ohnuma,¹ Tadanori Yamochi,^1,2 Masahiko Uchiyama,¹ Kunika Nishibashi,¹ Satoshi Iwata,¹ Osamu Hosono,¹ Hiroshi Kawasaki,¹ Hirotoshi Tanaka,¹ Nam H. Dang,² and Chikao Morimoto^1*

Department of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan,¹ Department of Lymphoma/Myeloma, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030²

Received 10 March 2005/ Returned for modification 8 April 2005/ Accepted 30 May 2005

CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of recombinant soluble CD26 resulted in enhanced proliferation of human T lymphocytes induced by the recall antigen tetanus toxoid (TT) via upregulation of CD86 on monocytes and that caveolin-1 was a binding protein of CD26, and the CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as well as TT-mediated T-cell proliferation. However, the mechanism involved in this immune enhancement has not yet been elucidated. In the present work, we perform experiments to identify the molecular mechanisms by which p-cav-1 leads directly to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll-interacting protein) and IRAK-1 (interleukin-1 receptor-associated serine/threonine kinase 1) as caveolin-1-interacting proteins in monocytes. We also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-B. Binding of CD26 to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells to induce antigen-specific T-cell proliferation.

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* Corresponding author. Mailing address: Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-354-495-546. Fax: 81-354-495-448. E-mail: morimoto{at}ims.u-tokyo.ac.jp.

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Molecular and Cellular Biology, September 2005, p. 7743-7757, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7743-7757.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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