Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain

Biochem Biophys Res Commun. 2003 Jan 10;300(2):291-6. doi: 10.1016/s0006-291x(02)02836-x.


Interleukin 21 (IL-21) is a recently identified novel cytokine that plays an important role in the regulation of B, T, and NK cell functions. Its effects depend on binding to and signaling through an IL-21 receptor complex consisting of the IL-21 receptor (IL-21R) and the common gamma-chain (gamma(c)). In this study using biosensor technique, the ligand-binding properties of IL-21R and gamma(c), which are presently poorly understood on a molecular level, were analyzed employing recombinant ectodomains of IL-21R and gamma(c). The formation of a binary complex between IL-21 and immobilized IL-21R (K(D) 70pM), gamma(c) and immobilized IL-21 (K(D) 160 microM) and a ternary complex between gamma(c) and IL-21 saturated immobilized IL-21R (K(D) 160nM) could be analyzed. The gamma(c) residues involved in IL-21 binding were defined by alanine-scanning mutational analysis. The epitope comprises gamma(c) residues N44, Y103, N128, L161, E162, and L208. It is not identical but partially overlapping with the previously established gamma(c) epitope for IL-4 binding. These results open the way to understand the molecular recognition mechanism in the IL-21 receptor system and also the promiscuous binding properties of gamma(c).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Epitopes / chemistry
  • Epitopes / metabolism
  • Humans
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-21 Receptor alpha Subunit
  • Interleukin-4 / chemistry
  • Interleukin-4 / metabolism*
  • Interleukins / chemistry
  • Interleukins / metabolism*
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Tertiary
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-21
  • Receptors, Interleukin-7 / chemistry*
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / metabolism*
  • Sequence Alignment


  • Epitopes
  • IL21R protein, human
  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • Macromolecular Substances
  • Receptors, Interleukin
  • Receptors, Interleukin-21
  • Receptors, Interleukin-7
  • Interleukin-4
  • interleukin-21