Analysis of TSA-1 that regulates TCR-mediated signal transduction

• Project/Area Number: 08839014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 免疫の制御機構
• Research Institution: Osaka University
• Principal Investigator: KOSUGI Atsushi Osaka University Medical School, Associate Professor, 医学部, 助教授 (90186685)
• Project Period (FY): 1996 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥1,900,000 (Direct Cost: ¥1,900,000); Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: T cells / T cell Receptor / TSA-1 / src-family kinases / DIG / CD3zeta / LCK / CD35鎖 / GPIアンカー型タン白質 / シグナル伝達 / 物理的会合

Research Abstract

Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 (Sca-2) is a glycosyl-phosphatidylinositol (GPI) -anchored antigen expressed on lymphocytes. We have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell receptor (TCR)-medialted T cell activation and apoptosis. To elucidate a molecular mechanism for TSA-1-mediated modulation of the TCR signaling pathway, we examined whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was clearly associated with CD3zeta chains in T cell hybridomas, activated T cells, and COS-7 cells transfected with TSA-1 and CD3zeta cDNA.The physical association was confirmed on the surface of T cells in immunoprecipitation and confocal microscopy. The analysis using stable and transient transfectants expressing a transmembrane form of TSA-1 revealed that the association of CD3zeta did not require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists. These results imply that the physical association to CD3zeta underlies a regulatory role of TSA-1/Sca-2 in TCR signaling pathway.

Research Products

• [Publications] Kosugi, A., et al.: "Physical and functional association between thymic shared antigen-I(TSA-1)lstem cell antigen -2(Sca-2)and the T cell receptor(TCR)complex." J.Biol.Chem.(印刷中). (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kosugi, A., et al.: "Subunit composition of the pre-T-cell receptor complex analyzed by monoclonal antibody against the pre-T-cell receptor α chain." Immunology.91. 618-622 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Abe, Y., et al.: "A defect in cell-to-cell adhesion via integrin-fibronectin interactions in a highly metastatic tumor cell line" Jpn.J.Cancer Res.88. 64-71 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Furuyama, T., et al.: "Identification of a novel transmembrane-type member of semaphorins expressel on lymphocytes." J.Biol.Chem.271. 33376-33381 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Noda, S., et al.: "Protection from anti-TCR/CD3 induced apoptosis in immoture thymaytes by a signal through thymic shared antigen-1/stem cell antigen-2." J.Exp.Med.183. 2355-2360 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kosugi, A., Saitoh, S.-I., Noda, S., Miyake, K., Yamashita, Y., Kimoto, M., Ogata, M., and Hamaoka, T.: "Physical and functional association between thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2) and the T cell receptor (TCR) complex." J.Biol.Chem.(in press.). (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kosugi, A., Noda, S., Saitoh, S.-I., Narumiya, S., Ogata, M., Hashimoto, Y., Takase, K., Saito, T.and Hamaoka, T.: "Subunit composition of the pre-T-cell receptor complex analyzed by monoclonal antibody against the pre-T-cell receptor alpha chain." Immunology.91. 618-622 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Abe, Y., Tsutsui, T., Mu, J., Kosugi, A., Yagita, H., Sobue, K., Niwa, O., Fujiwara, H.and Hamaoka, T.: "A defect in cell-to-cell adhesion via integrin-fibronectin interactions in a highly metastatic tumor cell line." Jpn.J.Cancer Res.88. 64-71 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Noda, S., Kosugi, A., Saitoh, S-I,Narumiya, S., and Hamaoka, T.: "Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2." J.Exp.Med.183. 2355-2360 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Furuyama, T., Inagaki, S., Kosugi, A., Noda, S., Saitoh, S.-I., Ogata, M., Iwahashi, Y., Miyazaki, N., Hamaoka, T., and Tohyama, M.: "Identification of a novel transmembrane semaphorin expressed on lymphocytes." J.Biol.Chem.271. 33376-33381 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] A.Kosugi et al.: "Subunit composition of the pre-T-cell receptor complex analyzod by monoclonal antibody against the pre-T-cell receptor chain." Immunology. 91. 618-622 (1997)
• [Publications] Y.Abe et al.: "A defect in cell-to-cell adhesion via integrin-fibronectin interactions in a highly meastatic tumor cell line." Jpn.J.Cancer Res.88. 64-71 (1997)
• [Publications] S.Noda et al.: "Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymiuc shared antigen-1/stem cell antigen-2." J.Exp.Med.183. 2355-2360 (1996)
• [Publications] T.Furuyama et al.: "Identification of a novel transmembrane semaphorin expressed on lymphocytes." J.Biol.Chem.271. 33376-33381 (1996)