Chimera of IL-2 linked to light chain of anti-IL-2 mAb mimics IL-2/anti-IL-2 mAb complexes both structurally and functionally

ACS Chem Biol. 2013 May 17;8(5):871-6. doi: 10.1021/cb3007242. Epub 2013 Mar 5.


IL-2/anti-IL-2 mAb immunocomplexes were described to have dramatically higher activity than free IL-2 in vivo. We designed protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly(4)Ser)(3). This protein chimera mimics the structure of IL-2/S4B6 mAb immunocomplexes but eliminates general disadvantages of immunocomplexes like possible excess of either IL-2 or anti-IL-2 mAb and their dissociation to antibody and IL-2 at low concentrations. This novel kind of protein chimera is characterized by an intramolecular interaction between IL-2 and binding site of S4B6 mAb similarly as in IL-2/S4B6 mAb immunocomplexes. Our protein chimera has biological activity comparable to IL-2/S4B6 mAb immunocomplexes in vitro, as shown by stimulation of proliferation of purified and activated OT-I CD8(+) T cells. The protein chimera exerts higher stimulatory activity to drive expansion of purified CFSE-labeled OT-I CD8(+) T cells activated by an injection of a low dose of SIINFEKL peptide than IL-2/S4B6 mAb immunocomplexes in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / genetics*
  • Antibodies, Monoclonal / metabolism
  • Base Sequence
  • Binding Sites
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CHO Cells
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Epitopes / genetics
  • Immunoglobulin Fc Fragments / genetics
  • Interleukin-2 / genetics*
  • Interleukin-2 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Mimicry
  • Molecular Sequence Data
  • Ovalbumin / pharmacology
  • Peptide Fragments / pharmacology
  • Protein Engineering
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology*


  • Antibodies, Monoclonal
  • Epitopes
  • Immunoglobulin Fc Fragments
  • Interleukin-2
  • OVA-8
  • Peptide Fragments
  • Recombinant Proteins
  • Ovalbumin