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1997 Fiscal Year Final Research Report Summary

Structural and Functional Analysis of Human Interleukin-12 Receptor

Research Project

Project/Area Number 08670514
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KAWASAKI Hiroshi  The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (80280957)

Co-Investigator(Kenkyū-buntansha) HOSONO Osamu  The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (50190210)
MORIMOTO Chikao  The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (30119028)
Project Period (FY) 1996 – 1997
Keywordsmolecular biology / Immunology / cytokine / receptor / signal transduction / monoclonal antibody / PCR
Research Abstract

We established a panel of monoclonal antibodies(mAb)to human Interleukin-12 receptor beta1chain(IL-12R)by Signal Trap method. In this case, the cDNA for Tac signal sequence was replaced with IL-12R signal+extracellular domain sequence. The chimeric cDAN was expressed and anti-Tac antibody was used to detect the chimeric protein. The transfected cells were used for immunization. Hybridomas were derived by conventional cell fusion and confirmed by positive staining with transfectants and negative with wild-type cells. We could obtain both neutralizing and non-neutralizing antibodies as determined by inhibition of IL-12 induced T cell proliferation assay and of radiolabelled ligand binding study. Immunoprecipitation disclosed putative p110 both from transfectants and PHA-stimulated human lymphocytes.
We could draw the following conclusions on IL-12 and IL-12R with newly developed mAb.
・T CELL responsiveness TO IL-12 required presence of monocytes and other antigen presenting cells. To be more specific, interaction between CD2 onT cells and CD58 on monocytes was essential in the T cell activation by IL-12
・T cell responsiveness to IL-12 was inhibited by IL-4 and enhanced by gammaIFN.Expression level of IL-12R on T cells was, however, not affected by either of cytokines.
・We could co-immunoprecipitate 85 kDa protein along with IL-12R from T cells with our mAb. This newly identified protein was tyrosine-phosphorylated upon IL-12 stimulation. This was different from other known STAT and JAK proteins. This molecule could be an interesting clue to analyze IL-12/IL-12R signal transduction system.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Gollob, JA: "Molecular Interaction Between CD-58 and CD2 Counter-Receptors Mediates t-he Ability of Monocytes to Augment TcellAcitvation by IL-12" Journal of Immunology. 157. 1886-1893 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gollob, JA: "Interferon-γ and Interleukin-4 regulate Tcell Interleukin-12 respons-iveness through the differential modula-tion of IL-12R" European Journal of Immunology. 27. 647-652 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawashima, T: "Interleukin-12 induees phosphory-lation of 85Kd cell surface protein ass-ociated with the Interleukin-12R β1 subunit" Cellular Immunology. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe, T: "Surrogate Thrombopoietin" Biochemical and Biophysical Rese-arch Communication. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] ・Gollob JA,Li J., Kawasaki H., Daley JF., Groves C., Reinnerz EL., and Ritz J.: ""Molecular Interactio Between CD58 and CD2 Counter-Receptors Mediates the Ability of Monocytes to Augment T Cell Activation by IL-12"" Journal of Immunology. 157. 1886-1893 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ・Gollob JA., Kawasaki H., and Ritz J.: ""Interferon-gamma and Interleukin-4 regulate T cell IL-12 responsiveness through the differential modulation of high-affinity IL-12 receptor expression"" European Journal of Immunology. 27. 647-652 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ・Kawashima H., Kawasaki H., Kitamura T., Nojima Y., and Morimoto C.: ""Interleukin-12 induces tyrosinephosphorylation of an 85 kDa cell surface protein associated with the Interleukin-12 receptor beta1 subunit"" Cellular Immunology. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ・Abe M., Yano S., Sakaba N., Kitamura K., Urasaki., Kawasaki H.: ""Surrogate Thrombopoietin"" Biochemical and Biophysical Reearch Communication. (in press). (1998)

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

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Published: 1999-03-16  

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