• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Development of specific imuune regulatoly drugs by the cell surface molecules.

Research Project

Project/Area Number 10557049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 内科学一般
Research InstitutionThe University of Tokyo

Principal Investigator

MORIMOTO Chikao  Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (30119028)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Hiroshi  Institute of Medical Science, The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (80280957)
HOSONO Osamu  Institute of Medical Science, The University of Tokyo, Assistant Professor, 医科学研究所, 助手 (50190210)
TANAKA Hirotoshi  Institute of Medical Science, The University of Tokyo, Associates Professor, 医科学研究所, 助教授 (00171794)
TANAKA Toshiaki  Toray Industries, Inc., Group Leader (researcher), 基礎研究所, 主任研究員
Project Period (FY) 1998 – 1999
KeywordsCD26 / dipeptidyl peptidase IV / adenosine deaminase / T cell costimulation / mannose 6-phosphate / insulin-like growth factor II receptor / mannose 6-phosphate / マンノース6リン酸
Research Abstract

CD26 is the T cell activation antigen and also known to bind the adenosine deaminase (ADA) and have a dipeptidyl peptidase IV (DPPIV) activity. Cross-linking of CD26 and CD3 with immobilized monoclonal antibodies can deliver a second costimulatory signal and contribute to T cell activation. Our earlier studies revealed that the cross-linking of CD26 induced internalization of the molecules, subsequent tyrosine phosphorylation of signaling molecules and resulted in an enhanced proliferating responses of T cells. Although these findings suggests the importance of internalization in the function of CD26. CD26 has only 6 amino acid residues in its cytoplasmic region with no known motif for endocytosis. In this study, we have identified the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) as the binding protein for CD26, and the mannose 6-phosphate (M6P) residues in carbohydrate moiety of CD26 is critical for the binding between CD26 and M6P/IGFIIR. In human peripheral blood lymphocytes, T cell activation resulted in the mannose 6-phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26 antibody induced not only capping and internalization of CD26 but also colocalization of CD26 with M6P/IGFIIR. Finally, internalization of CD26 by cross-linking and T cell proliferation induced by CD26 mediated T cell costimulation were inhibited by the addition of M6P, but not by the glucose 6-phosophate or mannose 1-phosphate. These results indicate that the interaction between mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26-mediated T cell constimulatory signaling.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Iwata S, Yamaguchi N, Munakata Y, Ikushima H, Lee JF, Hosono O, Schlossman SF, and Morimoto C.: "CD26/DPPIV differentially regulates the chemotaxis of T cells and monocytes toward RANTES"Int. Immunol. 11. 417-426 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Munakata Y, Umezawa Y, Iwata S, Dong R-P, Yoshida S, Ishii T and Morimoto C.: "Specific inhibition of Th2 type cytokine production from human peripheral T cells by terfenadine in vitro"Clin. Exp. Allergy. 29. 1281-1286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hosono O, Homma T, Kobayashi H, Munakata Y, Nojima Y, Iwamoto A, and Morimoto C.: "Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals"Clin. Immunol.. 91. 295 (283)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamiguchi K, Tachibana K, Ohashi Y, Fujita H, Iwata S, and Morimoto C.: "Cas-L is required for β1 integrin-mediated costimulation in T cells"J. Immunol.. 163. 563-568 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohashi Y, Iwata S, Kamiguchi K, Morimoto C.: "Tyrosine Phosphorylation of Cas-L is a Critical Element for T Cell Receptor- and β1 Integrin-induced T Lymphocyte Migration"J. Immunol.. 163. 3727-3734 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwata S, and Morimoto C.: "CD26/Dipeptidyl peptidase IV in context: The different roles of a multifunctional ectoenzyme in malignant transformation"J. Exp. Med.. 190. 301-305 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwata S, Yamaguchi N, Munakata Y, Ikushima H, Lee JF, Hosono O, Schlossman SF, and Morimoto C.: "CD26/DPPIV differentially regulates the chemotaxis of T cells and monocytes toward RANTES."Int. Immunol.. 11. 417-426 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Munakata Y, Umezawa Y, Iwata S, Dong R-P, Yoshida S, Ishii T and Morimoto C.: "Specific inhibition of Th2 type cytokine production from human peripheral T cells by terfenadine in vitro."Clin. Exp. Allergy. 29. 1281-1286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hosono O, Homma T, Kobayashi H, Munakata Y, Nojima Y, Iwamoto A, and Morimoto C.: "Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals."Clin. Immunol.. 91. 283-295 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamiguchi K, Tachibana K, Ohashi Y, Fujita H, Iwata S, and Morimoto C.: "Cas-L is required for β1 integrin-mediated costimulation in T cells."J. Immunol.. 163. 563-568 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohashi Y, Iwata S, Kamiguchi K, Morimoto C: "Tyrosine phosphorylation of Cas-L is a Critical Element for T Cell Receptor- and β1 Integrin-induced T Lymphocyte Migration."J. Immunol.. 163. 3727-3734 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwata S, and Morimoto C: "CD26/Dipeptidyl peptidase IV in context. The different roles of a multifunctional ectoenzyme in malignant transformation."J. Exp. Med.. 190. 301-305 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi