Comparison of Interleukin-22 and Interleukin-10 Soluble Receptor Complexes

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Abstract
Interleukin-22 (IL-22) is a cellular homolog of IL-10 that stimulates the production of acute-phase reactants. IL-22 and IL-10 require different ligand-specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain (IL-10R2) to initiate cellular responses. The quaternary structures and the ability of IL-22 and IL-10 to engage soluble (s) IL-10R1, IL-22R, IL-10R2 receptor chains were analyzed using size exclusion chromatography and surface plasmon resonance techniques. In contrast to IL-10, which is a homodimer, IL-22 is a monomer in solution that forms a 1:1 interaction with sIL-22R. Kinetic binding data reveal sIL-22R and sIL-10R1 exhibit specific nanomolar binding constants for IL-22 (kon/koff = 14.9 nM) and a monomeric isomer of IL-10 (IL-10M1) (kon/koff = 0.7 nM), respectively. In contrast, IL-10R2 exhibits essentially no affinity for IL-22 (Keq ~ 1 mM) or IL-10M1 (Keq ~ 2 mM) alone but displays a substantial increase in affinity for the IL-10/sIL-10R1 (Keq ~ 350 μM) and IL-22/sIL-22R (Keq ~ 45 μM) complexes. Three-dimensional models of IL-22 and IL-10 receptor complexes suggest two receptor residues (Gly-44 and Arg-96) are largely responsible for the marked differences in ligand affinity observed for sIL-10R1 and sIL-22R vs. sIL-10R2.