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Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling

Nature volume 369, pages 330–333 (1994)Cite this article

Abstract

THE interaction of interleukin-2 (IL-2) and IL-2 receptors criti-cally regulates the T-cell immune response following antigen activation1,2. IL-2 can signal through high or intermediate affinity receptors which contain IL-2Rα (refs 3, 4) + β (refs5–8) + γ (ref. 9) or β + γ chains, respectively. IL-2Rγ is a common γ chain, γc, also shared by the IL-7 (ref. 10) and IL-4 (refs 11,12) receptors, which when mutated results in X-linked severe combined immunodeficiency13. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the β- and γc-chain cytoplasmic domains. Anti-I L-2Rα monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracel-lular domains of IL-2Rβ and γc are replaced by that of IL-2Rα. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2Rα and that the β-transmembrane domain is not required for receptor chain inter-actions. Finally, we provide a method for mapping residues in the γc cytoplasmic domain even in cells that constitutively express γc.

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Author information

Author notes

  1. Yoshlaki Nakamura

    Present address: Second Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan

  2. Sarah A. Mess

    Present address: University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

  3. Michael Erdos

    Present address: National Center for Human Genome Research, NIH, Bethesda, Maryland, 20892, USA

  4. Stephen Adelstein

    Present address: Department of Immunology, Allergy and Infectious Disease, The St George Hospital, Kogarah, New South Wales, 2217, Australia

Affiliations

  1. Section on Pulmonary and Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bid. 10, Rm 7N244, Bethesda, Maryland, 20892, USA

    Yoshlaki Nakamura, Sarah M. Russell, Sarah A. Mess, Michael Friedmann, Michael Erdos, Stephen Adelstein & Warren J. Leonard

  2. INSERM Unite 211, Institut de Biologie, 9 Quai Moncousu, 44035, Nantes Cedex, France

    Christine Francois, Yannick Jacques & Stephen Adelstein

Authors
  1. Yoshlaki Nakamura
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  2. Sarah M. Russell
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  3. Sarah A. Mess
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  4. Michael Friedmann
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  6. Christine Francois
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  7. Yannick Jacques
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  8. Stephen Adelstein
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  9. Warren J. Leonard
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Nakamura, Y., Russell, S., Mess, S. et al. Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling. Nature 369, 330–333 (1994). https://doi.org/10.1038/369330a0

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