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The Role of IL-2 Receptor Alpha and Beta Chain in Growth and Differentiation of Lymphocytes

Research Project

Project/Area Number 01480185
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionTohoku University

Principal Investigator

SUGAMURA Kazuo  Tohoku University School of Medicine, Departmen of Microbiology, Professor, 医学部, 教授 (20117360)

Co-Investigator(Kenkyū-buntansha) TAKESHITA Toshikazu  Tohoku University School of Medicine, Department of Microbiology, Fellowships fo, 特別研究員 (60212023)
NAKAMURA Masataka  Tohoku University School of Medicine, Department of Microbiology, Lecturer, 医学部, 講師 (30180392)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1990: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsIL-2 / IL-2 receptor / lymphocytes / monocytes / receptor subunits / tyrosine kinase / monoclonal antibody / flow cytometry / ILー2受容体 / 胸腺細胞 / CD4 / CD8 / NK細胞 / IL-2受容体 / チロシン・キナ-ゼ
Research Abstract

We established two monoclonal antibodies (TU27mAb and TU11mAb) specific for the human IL-2 receptor (IL-2R) beta chain. TU27mAb inhibited IL-2-binding to IL-2Rbeta but not TU11mAb. Peripheral blood leukocytes were examined for expression of the IL-2Ralpha and beta chains by two-color flow cytometric analyses using mAbs. NKH-1^+ non-T non-B cells expressed IL-2Rbeta but not IL-2Ralpha. In CD4^+T cells, IL-2Ralpha^+ cells were significantly detected, but little or marginally of the IL-2Rbeta^+ cells. However, IL-2Rbeta^+ cells were significantly detected, but little of the IL-2Ralpha^+ cells in CD8^+T cells. IL-2Rbeta^+ cells, but not IL-2Ralpha^+ cells, were also detected in CD14^+ monocytes. In CD20^+B cells, a small number of IL-2Ralpha^+ cells was detected, but little of the IL-2Rbeta^+ cells.
TU11mAb co-precipitated two molecules, p64 and p55, with IL-2Rbeta in the lysates of IL-2R-bearing cells in the presence of IL-2 even in the absence of a chemical cross-linker. The peptide maps indicate that p64 is a molecule distinct from both IL-2Ralpha and IL-2Rbeta, and that p55 is identical to IL-2Ralpha. These findings suggest that p64, along with IL-2Ralpha and IL-2Rbeta, is a component of the IL-2R complex, and we have tentatively named it the gamma-chain of IL-2R.
Using TU11mAb, we also demonstrated the IL-2-induced phosphorylation of IL-2Rbeta on tyrosine residues in IL-2-dependent T cells. The tyrosine phosporylation correlates with the IL-2-induced cell growth, and rapidly increases during the first 5 min of IL-2 stimulation. These results suggest some roles of a tyrosine kinase associated with IL-2Rbeta in the IL-2-induced signal-transductng pathway.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] Takeshita,T.: "Monoclonal antibody defining a moleculepossibly identical to the p75 subunit ofinterleukin 2 receptor" J.Exp.Med.169. 1323-1332 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nagata,K.: "Activation of endogenous cーfos protoーoncongene expression by human Tーcell leukemia virus type Iーencoded p40tax protein in a human Tーcell line Jurkat" J.Virol.63. 3220-3226 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki,J.: "ILー2 receptor subunit,p75:direct demonstration of its ILー2 binding ability by using a novel monocloanl,antibody" Int.Immunol.1. 373-377 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] philips,J.H.: "Activation of NK cells Via the p75 interleukin2 receptor" J.Exp.Med.170. 291-296 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohashi,Y.: "Differential expression of the receptor,subunits,p55 and p75 on various populations of primary peripheral blood mononuclear cells" J.Immunol.143. 3548-3555 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Allouche,M.: "Presence of a p70 ILー2 binding peptide on leukemic cells from various hematopoietic lineages" J.Immunol.143. 2223-2229 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yagita,H.: "Activation of peripheral blood T cells via the p75 interleukinー2 receptor" J.Exp.Med.170. 1445-1450 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asao,H.: "Interleukin 2 (ILー2)ーinduced tyrosine phsphorylation of ILー2 receptor p75" J.Exp.Med.171. 637-644 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ortaldo,J.R.: "Regulation of CD3^- lymphocyte function with an antibody against the ILー2betaーchain receptor:modulation of NK and LAKactivity and production of IFNーgamma" Eur.Cytokine Net.1. 27-34 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asao,H.: "The evidence for the ILー2 receptor beta chain processing from p70 to p75" Int.Immunol.2. 470-472 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Takeshita,T.: "An associated molecule,p64,with highーaffinity interleukin 2 receptor" Int.Immunol.2. 477-480 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nishikawa,K.: "Differential expression of the interleukin 2 receptor beta (p75) chain on humanperipheral blood natural killer subsets" Int.Immunol.2. 481-486 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] EspinozaーDelgado,I.: "Expression and role of p75 interleukin 2 receptor on human monocytes" J.Exp.Med.171. 1821-1826 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] WeilーHillman,G.: "Natural killer cells activated by interleukin 2 primarily through the p75 receptor and maintain the p55 (Tac) negative phenotype" Cancer Res.50. 2683-2691 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Takeshi,T.: "Establishment of cyclic AMPーdependent growing human T cell line derived from aninterleukin 2ーdependent cell line" J.Cell.Physiol.145. 238-243 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Voss,S.D.: "Increased expression the ILー2 receptor beta chain (p70 on CD56^+ NK cells following in vivo ILー2 therapy:p70 expression dose not alone predic the level of intermediateーaffinity ILー2 bidning" J.Exp.Med.172. 1101-1114 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Honda,M.: "Identification of a soluble ILー2receptor beta chain from human lymphoid cell line cells" J.Immunol.145. 4131-4135 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Takeshita, T. et al.: "Monoclonal antibody defining a molecule possibly identical to the p75 subunit of interleukin 2 receptor" J. Exp. Med.169,. 1323-1332 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nagata, K. et al.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in a human T-cell line Jurkat" J. Virol.63,. 3220-3226 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, J. et al.,: "IL-2 receptor subunit, p75 : direct demonstration of its IL-2 binding ability by using a novel monoclonal antibody" Int. Immunol.,. 1,. 373-377 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Philips, J. H. et al.,: "Activation of NK cells via the p75 interleukin 2 receptor" J. Exp. Med.,. 170. 291-296 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohashi, Y. et al.,: "Differential expression of the interleukin 2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells" J. Immunol.143,. 3548-3555 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Allouche, M. et al.,: "Presence of a p70 IL-2-binding peptide on leukemic cells from various hematopoietic lineages" J. Immunol.143,. 2223-2229 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yagita, H. et al.,: "Activation of peripheral blood T cells via the p75 interleukin-2 receptor" J. Exp. Med.170,. 1445-1450 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asao, H. et al.,: "Interleukin 2 (IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75" J. Exp. Med.,. 171,. 637-644 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ortado, J. R. et al.: "Regulation of CD3^- lymphocyte function with an antibody against the IL-2R beta-chain receptor : modulation of NK and LAK activity and production of IFN-gamma" Eur. Cytokine Net.1. 27-34 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asao, H. et al.,: "The evidence for the IL-2 receptor beta chain processing from p70 to p75" Int. Immunol.2,. 470-472 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Takeshita, T. et al.,: "An associated molecule, p64, with high-affinity interleukin 2 receptor" Int. Immunol.2,. 477-480 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nishikawa, K. et al.: "Differential expression of the interleukin 2 receptor beta (p75) chain on human peripheral blood natural killer subsets" Int. Immunol.,. 2,. 481-486 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Espinoza-Delgado, I. et al.,: "Expression and role of p75 interluekin 2 receptor on human monocytes" J. Exp. Med.,. 171,. 1821-1826 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Well-Hillman, G. et al.,: "Natural killer cells activated by interleukin 2 treatment in vivo respond to interlekin 2 primarily through the p75 receptor and maintain the p55 (Tac) negative phenotype" Cancer Res.,. 50,. 2683-2691 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Takeshita, T. et al.,: "Establishment of a cyclic AMP-dependent growing human T cell line derived from an interleukin 2-dependent cell line" J. Cell. Physiol.145,. 238-243 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Voss, S. D. et al.,: "Increased expression of the IL-2 receptor beta chain (p70) on CD56^+ NK cells following in vivo IL-2 therapy : p70 expression dose not alone predict the levol of intermediate-affinity IL-2 binding" J. Exp Med.,. 172,. 1101-1114 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Honda, M. et al.,: "Identification of a soluble IL-2 receptor beta chain from human lymphoid cell line cells" J. Immunol.,. 145,. 4131-4135 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asao,H.: "Interleukinー2 (ILー2)ーinduced tyrosine phosphorylation of ILー2 receptor p75" J.Exp.Med.171. 637-644 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ortaldo,J.R.: "Regulation of CD3^- lymphocyte function with an antibody against the ILー2β chain receptor:modulation of NK and LAK activity and production of IFNーγ" Eur.Cytokine Net.1. 27-34 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Asao,H.: "The evidence for the ILー2 receptor β chain processing from p70 to p75" Int.Immunol.2. 470-472 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takeshita,T.: "An associated molecule,p64,with highーaffinity interleukin 2 receptor" Int.Immunol.2. 477-480 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nishikawa,K.: "Differential expression of the interluekin 2 receptor β (p75) chain on human peripheral blood natural killer subsets" Int.Immunol.2. 481-486 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] EspinozaーDelgado,I.: "Expression and role of p75 interleukin 2 receptor on human monocytes" J.Exp.Med.171. 1821-1826 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] WeilーHillman,G.: "Natural killer cells activated by interleukin 2 treatment in vivo respond to interleukin 2 primarily through the p75 receptor and maintain the p55 (Tac) negative phenotype" Cancer Res.50. 2683-2691 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takeshita,T.: "Establishment of a cyclic AMPーdependent growing human T cell line derived from an interleukin 2ーdependent cell line" J.Cell.Physiol.145. 238-243 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Voss,S.D.: "Increased expression of the ILー2 receptor β chain (p70) on CD56^+ NK cells following in vivo ILー2 therapy: p70 expression dose not alone predict the level of intermediateーaffinity ILー2 binding" J.Exp.Med.172. 1101-1114 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Honda,M.: "Identification of a soluble ILー2 receptor β chain from human lymphoid cell line cells" J.Immunol.145. 4131-4135 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takeshita,T.: "Monoclonal antibody defining a molecule possibly identical to the p75 subunit of interleukin 2 receptor" J.Exp.Med.169. 1323-1332 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Nagata,K.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in a hunan T-cell line Jurkat" J.Virol.63. 3220-3226 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suzuki,J.: "IL-2 receptor subunit,p75:direct demonstration of its IL-2 binding ability by using a novel monoclonal antibody" Int.Immunol.1. 373-377 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Philips,J.H.: "Activation of NK cells via the p75 interleukin 2 receptor" J.Exp.Med.170. 291-296 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ohashi,Y.: "Differential expression of the interleukin 2 receptor subunits,p55 and p75 on various populations of primary peripheral blood mononuclear cells" J.Immunol.143. 3548-3555 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Allouche,M.: "Presence of a p70 IL-2-binding peptide on leukemic cells from various hematopoietic lineages" J.Immunol.143. 2223-2229 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yagita,H.: "Activation of peripheral blood T cells via the p75 interleukin-2 receptor" J.Exp.Med.170. 1445-1450 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Asao,H.: "Interleukin 2(IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75" J.Exp.Med.

    • Related Report
      1989 Annual Research Report
  • [Publications] Espinoza-Delgado,I.: "Expression and role of p70-75 protein on human monocytes" J.Exp.Med.

    • Related Report
      1989 Annual Research Report
  • [Publications] Asao,H.: "The evidence for the IL-2 receptor β chain processing from p70 to p75" Int.Immunol.

    • Related Report
      1989 Annual Research Report
  • [Publications] Takeshita,T.: "An associated molecule,p64,with high-affinity interelukin 2 receptor" Int.Immunol.

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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