Ligand binding by the IL-2 receptor is modulated by intracellular determinants of the IL-2 receptor beta-chain

J Immunol. 1995 Mar 1;154(5):2033-40.


The biologic actions of IL-2 are mediated by the IL-2R, a multisubunit receptor complex displayed on the surface of lymphocytes and select other hematopoietic lineages. The IL-2R exhibits multiple affinities for IL-2 that result from the monomeric (alpha), heterodimeric (alpha beta and beta gamma), and heterotrimeric (alpha beta gamma) assembly of different receptor subunits. In the present studies, we have used a series of IL-2R mutants in a transient mammalian expression system to investigate the potential role of intracellular receptor regions in the ligand-binding functions of the IL-2R. Analyses of chimeric and deletion mutants of the IL-2R beta subunit have revealed that its intracellular domain critically and selectively influences high affinity ligand binding mediated through the extracellular domains of the alpha beta-heterodimeric receptor. In contrast, intermediate affinity binding of IL-2 by beta gamma-heterodimeric receptors exhibits no dependence on the cytoplasmic domain of IL-2 R beta. Further, co-expression of either a full-length or severely truncated form of IL-2 R gamma to generate an alpha beta gamma-heterotrimeric complex also overcomes the functional dependence upon the cytoplasmic tail of IL-2 R beta. Collectively, our findings suggest that the cytoplasmic domain of IL-2R beta produces intrasubunit transmembrane conformational changes in this receptor subunit that promote extracellular IL-2 binding in combination with IL-2R alpha. These findings have important implications for the receptor dynamics involved in both ligand binding and signal transduction as well as for clinical applications pertaining to altering IL-2R function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • Cytoplasm / metabolism
  • Interleukin-2 / metabolism
  • Kinetics
  • Ligands
  • Mutation
  • Protein Conformation
  • Receptors, Interleukin-2 / chemistry
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Transfection


  • Interleukin-2
  • Ligands
  • Receptors, Interleukin-2