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Structure of and signal transduction through T cell receptor complex

Research Project

Project/Area Number 04454206
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

SAITO Takashi  Chiba University School of Medicine, Professor, 医学部, 教授 (50205655)

Co-Investigator(Kenkyū-buntansha) OHNO Hiroshi  Chiba University School of Medicine, Research Associate, 医学部, 助手 (50233226)
MIYATAKE Shoichiro  Chiba University School of Medicine, Research Associate, 医学部, 助手 (30239420)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1992: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsT cell antigen receptor / CD3 complex / Intracellular signal transduction mechanism / CD3zeta family molecules / TCRbeta dimer expression / Signaling motif / PLCgamma1 / Tyrosine phosphorylation / CD3ξファミリー分子 / T細胞レセプター / ζファミリー分子 / シグナル伝達 / チロシンキナーゼ / シグナルモチーフ / ζダイマーレセプター
Research Abstract

There is structural heterogeneity of the T cell receptor-CD3 complex based on the different composition of TCR dimeers or CD3zeta dimers. In vivo, different T cell subsets on differentiation stages possess such different structures. We have analyzed the relationship between the TCR structure and signal transduction.
(1)An immature thymocyte cell line KKF expresses only TCRbeta but not other TCR chains which is associated with CD3 complex on the cell surface. KKFbeta is not special. Transfection of other TCRbeta induced the cell surface expression of the transfected beta chains. The beta dimer associates very weakly with CD3 chains especially with the zeta chain. Introduction of the TCRalpha chain resulted in the expression of only alphabeta dimer which is associated with CD3 chains as strongly as mature T cells. These suggest that beta dimer-expressing thymocytes may be the precursors of alphabeta T cells.
(2)Signal transduction through different TCR isoforms containing different zeta fa … More mily molecules (zeta, eta, FcRgamma) was compared. Any TCR complexes expressing dimeers of zeta, eta or FcRgamma produced IL-2 upon antigen stimulation. However, FcRgamma+ TCR failed to induce activation induced growth inhibiton, whereas eta+TCR did not respond to Thy-1 stimulation. Thus, signals mediated via defferent zeta family molecules appear to be different.
(3)We generated mutant zeta lacking signal motifs to investigate the function of the motif commonly present in CD3 chains. TCR complex lacking zeta motifs could produce IL-2 upon antigen stimulation but did not respond to Thy-1 stimulation. Patterns of tyrosine phosphorylation also differ between the wild-type and mutant zeta. Therefore, there are two types of signals generated through the TCR-CD3 complex ; one through the common signal motifs, the other through strictly zeta family molecules.
(4)According to the analysis of T cell transfectants expressing PDGF receptors, activation of PLCgamma and the PI pathway is not enough to produce IL-2 and co-operation with signals through tyrosine phosphorylation by TCR will be required. Less

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Ohno,H.: "Developmental and functional impairment of T cells in mice lacking CD3ζchains." The EMBO Journal. 12. 4357-4366 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno,H.: "TCR isoform containing the Fc receptor γ chain exhibits structural and functional differences from isoform containg CD3ζ." International Immunology. 5. 1403-1411 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno,H.: "Preferential usage of the FcRγ in the T cell antigen receptor complex by γδT cells localized in epithelia." Journal of Experimental Medicine. 179. 365-369 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno,H.: "Targeted disruption of the CD3η locus causes high lethality in mice:Modulation of Oct-1 transcription on the opposite strand." The EMBO Journal. (in press.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuwabara,I.: "Transition from TCRβ dimer- to TCRαβ-expressing cells by introduction of an α chain in an immature thymocyte cell line." Journal of Immunology. (in press.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakano,H.: "Activation of phospholipase C-γ1 through transfected platelet-derived growth factor receptor enhances interleukin 2 production upon antigen stimulation in a T-cell line." Molecular and Cellular Biology. 14. 1213-1219 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno, H: "Developmenta and functional impairment of T cells in mice lacking CD3zeta chains." The EMBO Journal. 12. 4357-4366 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno, H: "TCR isoform containing the Fc receptor gamma chain exhibits structural and functional differences from isoform containg CD3zeta." International Immunology. 5. 1403-1411 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno, H: "Preferential usage of the FcRgamma in the T cell antigen receptor complex by gammadelta T cell localized in epithelia." Journal of Experimental Medicine. 179. 365-369 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno, H: "Targeted disruption of the CD3eta locus causes high lethality in mice : Modulation of Oct-1 transcription on the opposite strand." The EMBO Journal. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kuwabara, I: "Transition from TCRbeta dimer- to TCRalphabeta-expressing cells by introduction of an alpha chain in an immature thymocyte cell line." Journal of Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakano, H: "Activation of phospholipase C-gamma1 through transfected platelet-derived growth factor receptor enhances inerleukin 2 production upon antigen stimulation in a T-cell line." Molecular and Cellular Biology. 14. 1213-1219 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno,H.: "Developmental and functional impairment of T cells in mice lacking CD3ζ chains." The EMBO Journal. 12. 4357-4366 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohno,H.: "TCR isoform containing the Fc receptor γ chain exhibits structural and functional differences from isoform containg CD3ζ." International Immunology. 5. 1403-1411 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohno,H.: "Preferential usage of the FcRγ in the T cell antigen receptor complex by γδ T cells localized in epithelia." Journal of Experimental Medicine. 179. 365 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohno,H.: "Targeted disruption of the CD3η locus causes high lethality in mice:Modulation of Oct-1 transcription on the opposite strand." The EMBO Journal. (in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kuwabara,I.: "Transition from TCRβ dimer-to TCRαβ-expressing cells by introduction of an α chain in an immature thymocyte cell line." Journal of Immunology. (in press.).

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakano,H.: "Activation of phospholipase C-γ1 through transfected platelet-derived growth factor receptor enhances interleukin 2 production upon antigen stimulation in a T-cell line." Molecular and Cellular Biology. 14. 1213-1219 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Aoe, T., Ohno, H.,Sonta, S. and Saito,T.: "Functional inactivation of CD3ζ chain in a T cell hybridoma by in vitro gene targeting." Int.Immunol.,.

    • Related Report
      1992 Annual Research Report
  • [Publications] Hahn, W.C., Menzin, E.Saito, T., Germain, R.N. and Bierer, B.E.: "The complete nucleotide sequence of pFNeo and pMH-Neo:Convenient expression vectors for high level expression of eukaryotic genes in hematopoietic cell lines." Gene,.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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