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Development of immunoregulatory therapy via CD26 activation pathway.

Research Project

Project/Area Number 08557036
Research Category

Grant-in-Aid for Scientific Research (A)

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

Co-Investigator(Kenkyū-buntansha) HOMMA Toshio  The University of Tokyo Institute of Medical Science Research Associate, 医科学研究所, 教務職員 (10282526)
HOSONO Osamu  The University of Tokyo Institute of Medical Science Research Associate, 医科学研究所, 助手 (50190210)
KAWASAKI Hiroshi  The University of Tokyo Institute of Medical Science Research Associate, 医科学研究所, 助手 (80280957)
NOJIMA Yoshihisa  Gunma University school of Medicine Associate Professor, 医学部, 助教授 (90201699)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥15,900,000 (Direct Cost: ¥15,900,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1996: ¥12,500,000 (Direct Cost: ¥12,500,000)
KeywordsCD26 / Dipeptidyl peptidase IV / Adenosine deaminase / Costimulatory molecule / adenosine / Dipeptidyl peptidase IV / costimylatory分子 / ADA結合蛋白 / co-stimulatory分子 / CD3 / TCR複合体
Research Abstract

CD26, a 110-KDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV (DPPIV) enzyme activity and plays an important role in T cell costimulation. We previonsly demonstrated that CD26 is directly associated with adenosine deaminase (ADA) and that cells expressing ADA and CD26 on the surface were much more resistant to the inhibitory effect of adenosine, suggesting that ADA on the cell surface via CD26 appears to overcome the inhibitory effect of the elevated extracellular adenosine. However, previous studies have not yet determined whether there is a specific ADA binding domain on CD26, whether the interaction of ADA and CD26 on the cell surface has a direct immunoregulatory effecton T cell activation, and whether CD26 on the cell surface involves resistance to the inhibitory effect of adenosine.
We found that the residues of Leucine_<340>, Valine_<341>, Alanine_<342>and Arginine_<343> on the CD26 molecule were essential amino acids for ADA binding. When these amino acids were mutated and transfected into Jurkat cells, the resultant CD26 transfectants expressed only CD26, not ADA,on the cell surface. The amount of IL-2 produced by wild-type and mutated CD26 transfectants was almost the same following stimulation with anti-CD3 plus PMA.However, the mutated CD26 transfectants were much more sensitive to the inhibitory effect of adenosine on IL-2 production than were the wild CD26 transfectants. These data suggest that ADA on the cell surface does not directlyinvolve T cell activation. Conversely, CD26 alone does not result in modulating the inhibitory effect of adenosine. Only the ADA bound to CD26 on the cell surface was functional and could counteract the inhibitory effect of elevated extracellular adenosine.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Dong R-P.: "Correlation of the epitope defined by anti-CD26 mAbs and CD26 function" Mol.Immunol.発表予定.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong RP.: "Determination of adenosine deaminase binding domain on CD26 and its immunoregulatory effect on T cell activation." J.Immunol.159. 6070-6076 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong R-P.: "Different regulatory effects of pentoxifylline on human T cell activation pathway" J.Clin.Immunol.17. 247-252 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hegen M.: "Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase" Immunol.90. 257-264 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong R-P.: "Correlation of the epitope defined by anti-CD26 mAbs and CD26 function." Mol.Immunol.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong RP.: "Determination of adenosine deaminase binding domain on CD26 and its immunoregulatory effect on T cell activation." J.Immunol.159. 6070-6076 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong R-P.: "Different regulatory effects of pentoxifylline on human T cell activation pathways." J.Clin.Immunol.17. 247-252 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hegen M.: "Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase." Immunol.90. 257-264 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dong R-P.: "Correlation of the epitope defined by anti-CD26 mAbs and CD26 function." Mol.Immunol.(発表予定).

    • Related Report
      1997 Annual Research Report
  • [Publications] Dong RP.: "Determination of adenosine deaminase binding domain on CD26 and its immunoregulatory effect on T cell activation." J.Immunol.159. 6070-6076 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Dong R-P.: "Different regulatory effects of pentoxifylline on human T cell activation pathways." J.Clin.Immunol.17. 247-252 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hegen M.: "Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase." Immunol.90. 257-264 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Dong,R.: "Characterization of adenosine deaminase(ADA)binding to human CD26 on T cells and its biological role in immune response" J.Immunol. 156. 1349-1355 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Duke-Cohan,JS.: "Serum high molecular weight dipeptidyl peptidase IV(CD26)is identical to a novel antigen,DPPT-L,released from activated T cells" J.Immunol. 156. 1714-1721 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Falcioni,F.: "Influence of CD26 and integrins on the antigen sensitivity of human memory T cells" Human Immunol. 50. 79-90 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Dong,RP.: "Role of CD26 for CD4 memory T cell function and activation" Human Cell. 9. 153-162 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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