Intermolecular Cystine-Bonding of Murine Interleukin 2 Indicates that Ligand Dimerization is Important for the Formation of the High-Affinity Receptor Complex

Interleukin 2 is thought to be active as a monomeric protein. As the nonessential Cys-140 of murine interleukin 2 (mIL2) is located in the hydrophobic interface of the amphiphilic F domain it was successfully used to stabilize hydrophobic amino acid contacts between two mIL2 cores yielding biologically active cystine-bonded dimeric mIL2. (3H) thymidine incorporation assays with intermolecular cystine-bonded or monomeric mIL2 revealed almost identical median effective concentrations (EC50) and high-affinity dissociation constants (Kdh), respectively. Comparative binding and internalization assays suggest that one cystine-bonded dimeric or two monomeric mIL2 molecules bind to the high-affinit…