Quantitative characterization of the intrinsic ligand-binding affinity of the interleukin 2 receptor beta chain and its modulation by the alpha chain and a second affinity-modulating element

Lymphokine Cytokine Res. 1991 Jun;10(3):219-24.

Abstract

The interleukin 2 receptor is a multisubunit receptor known to consist of at least two IL-2 binding subunits, alpha and beta. We report here kinetic evidence defining the contribution of an affinity-modulating element(s) intimately involved in modulation of the ligand-binding affinity of the beta chain and alpha/beta complex. The principal effect of this modulating element on the beta chain is to slow the dissociation of IL-2 more than 150-fold and thus raise its low intrinsic IL-2 binding affinity (Kd = 70 nM) as defined in transfected fibroblast cells to the level observed in lymphoid cells (Kd = 1.2 nM). The alpha subunit also increases the ligand-binding affinity of the beta chain, although in this case principally by increasing the association rate constant more than 1200-fold. The additional effect of the affinity-modulating element on the alpha/beta complex is minimal with regards to the equilibrium binding affinity. It does, however, have a detectable 14-fold effect on slowing the IL-2 dissociation rate. The existence of multiple forms of IL-2 receptor complexes with widely varying ligand affinities and dissociation rates illustrates the need for careful evaluation of binding data in studies of receptor subunit composition and reconstitution.

MeSH terms

  • Animals
  • Cell Line
  • Gene Amplification
  • Humans
  • Interleukin-2 / metabolism*
  • Kinetics
  • Ligands
  • Macromolecular Substances
  • Protein Binding
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • Interleukin-2
  • Ligands
  • Macromolecular Substances
  • Receptors, Interleukin-2
  • Recombinant Proteins