Expression of interleukin 2 receptor subunits and mechanism of T cell growth

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 03454193
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: SUGAMURA Kazuo School of Medicine Microbiology Professor, 医学部, 教授 (20117360)
• Co-Investigator(Kenkyū-buntansha): ASAO Hironobu School of Medicine Microbiology Researcher, 医学部, 特別研究員 ; OHTANI Kiyoshi School of Medicine Microbiology Lecturer, 医学部, 助手 (30201974)
• Project Period (FY): 1991 – 1992
• Keywords: IL-2 / IL-2 receptor / gamma chain / high-affinity receptor

Research Abstract

Interleukin 2 (IL-2) is known to be a physiological soluble factor which affects proliferation and activation not only of T cells but of B cells,monocytes and glioma cells. IL-2 action is exerted through binding to cell surface specific IL-2 receptors. Two subunits, alpha and beta chains, have been identified so far. The beta chain, a component of the functional intermediate- and high-affinity receptors, is shown to be essential for delivery of intracellular signals. Several lines of evidence indicate that the alpha and beta molecules are not sufficient for the functional IL-2 receptors and suggest involvement of another lymphoid cell-specific factor. In this context, we have identified a 67KDa molecule (gamma chain) by co-immunoprecipitation with anti-beta chain antibody. The gamma chain is always associated with the intermediate-and high-affinity receptors but not the low-affinity receptor. After purification electrophoretically, the partial amino acid sequence of the gamma chain was determined and we succeeded in cloning of cDNA for the gamma chain. The gamma chain is a member of the cytokine receptor superfamily, although the gamma chain alone can not bind to IL-2,and expressed in various cells of hemotopoietic lineage. Transfection experiments with a fibroblast L cell line evidenced that the alpha beta gamma heterotrimer and the beta gamma heterodimer are the high-and intermediate- affinity receptors, respectively, both of which are able to mediate intracytoplasmic signals.

Research Products

• [Publications] Takeshita,T.: "An associated molecule,p64,with IL-2 receptor β chain:its possible involvement in formation of the functional IL-2 receptor complex." J.Immunol.148. 2154-2158 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sugamura,K.: "Expression of IL-2 receptor subunits,α,β and γ,on HTLV-I-transformed T cells." Gann Monograph on Cancer Research.39. 119-128 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asao,H.: "IL-2-dependent in vivo and in vitro tyrosine phosphorylation of IL-2 receptor γ chain." FEBS Letters. 304. 141-145 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takeshita,T.: "Cloning of the γ chain of the human IL-2 receptor." Science. 257. 379-382 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kumaki,S.: "Cell type-specific activation of a tyrosine kinase associated with IL-2 receptor β chain in response to IL-2." FEBS letters. 310. 22-26 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asao,H.: "Reconstitution of the functional IL-2 receptor complexes on fibroblastoid cells:Involvement of the cytoplasmic domain of the γ chain in two distinct signaling pathways." Proc.Natl.Acad.Sci.USA.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakamura,Y.,Nishimura,T.,Tokuda,Y.,Kobayashi,N.,Watanabe,K.,Noto,T.,Mitomi,T.,Sugamura,K. and Habu,S.: "Macrophage-T cell interaction is essential for the induction of p75 interleukin 2 (IL-2) receptor and IL-2 responsiveness in human CD4+ T cells." Jpn.J.Cancer Res.82. 257-261 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishikawa,K.,Saito,S.,Morii,T.,Hamada,K.,Hirofumi,A.,Narita,N.,Ichijo,M.,Kurahayashi,Y.,Sugamura,K.: "Accumulation of CD16-CD56^+ natural killer cells with high affinity interleukin 2 receptors in human early pregnancy decidua." Int.Immunol.3. 743-750 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ohbo,K.,Takeshita,T.,Asao,H.,Kurahayashi,Y.,Tada,K.,Mori,H.,Hatakeyama,M.,Taniguchi,T. and Sugamura,K.: "Monoclonal antibodies defining distinct epitopes of the human IL-2 receptor beta chain and their differential effects on IL-2 responses." J.Immunol.Methods. 142. 61-72 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeshita,T.,Ohtani,K.,Asao,H.,Kumaki,S.,Nakamura,M. and Sugamura,K.: "An associated molecule,p64, with IL-2 receptor beta chain: its possible involvement in formation of the functional IL-2 receptor complex." J.Immunol.148. 2154-2158 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sugamura,K.: "Expression of IL-2 receptor subunits, alpha, beta and gamma, on HTL V-I-transformed T cells." Gann Monograph on Cancer Research. 39. 119-128 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Asao,H.,Kumaki,S.,Takeshita,T.,Nakamura,M. and Sugamura,K.: "IL-2-dependent in vivo and in vitro tyrosine phosphorylation of IL-2 receptor gamma chain." FEBS Letters. 304. 141-145 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kumaki,S.,Asao,H.,Takeshita,T.,Kurahayashi,Y.,Nakamura,M.,Beckers,T.,Engels,J.W., and Sugamura,K.: "Cell type-specific activation of a tyrosine kinase associated with IL-2 receptor beta chain in response to IL-2." FEBS Letters. 310. 22-26 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeshita,T.,Asao,H.,Ohtani,K.,Ishii N.,Kumaki,S.,Tanaka,N.,Munakata,H.,Nakamura,M. and Sugamura,K.: "Cloning of the gamma chain of the human IL-2 receptor." Science. 257. 379-382 (1992)
  • Description: 「研究成果報告書概要(欧文)」より