Structure-function relationships for the IL 2-receptor system. II. Localization of an IL 2 binding site on high and low affinity receptors

J Immunol. 1986 Sep 1;137(5):1544-51.

Abstract

The ligand-binding component of high and low affinity IL 2 receptors is a 55,000 m.w. glycoprotein termed Tac. Correlating the structure and function of this molecule should provide insight into the mechanism of IL 2-initiated signal transduction and the structural basis for high and low affinity receptor forms. As a first step in this process, various approaches were used to localize the IL 2 binding region of the Tac molecule. Antibodies prepared to synthetic fragments of Tac were tested for their ability to interfere with IL 2 binding and bioactivity. The results delineated segments in the C-terminal portion of the molecule which appeared to be distal to the ligand binding site. In a more direct approach, radioiodinated IL 2 was cross-linked to high and low affinity receptors, and the resulting complexes were subjected to mild tryptic digestion. Consistent with the antibody data, the IL 2 remained covalently associated with an N-terminal tryptic fragment which apparently consisted of residues 1-83 of the Tac protein. These results suggest that the N-terminal region of the Tac molecule contains important contact sites for ligand-receptor interaction.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Antigens, Surface / analysis*
  • Antigens, Surface / immunology
  • Binding Sites
  • Cell Division / drug effects
  • Epitopes / immunology
  • Humans
  • Interleukin-2 / metabolism*
  • Interleukin-2 / pharmacology
  • Mice
  • Peptides / analysis
  • Protein Binding
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / immunology
  • Receptors, Interleukin-2
  • Structure-Activity Relationship
  • T-Lymphocytes / analysis*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Substances

  • Antibodies
  • Antigens, Surface
  • Epitopes
  • Interleukin-2
  • Peptides
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 7