Soluble heterodimeric cytokine receptor

Abstract

A soluble receptor that binds to IL-20 having two polypeptide subunits, IL-22R and IL-20RB. The two subunits are preferably linked together. In one embodiment one subunit is fused to the constant region of the light chain of an immunoglobulin, and the other subunit is fused to the constant region of the heavy chain of the immunoglobulin. The light chain and the heavy chain are connected via a disulfide bond.

What is claimed is:  
     
         1 . An isolated soluble receptor comprised of an IL-22R subunit and a IL-20RB subunit, wherein the IL-22R subunit is comprised of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 12, 13, 25, 26 31 and 32, and the IL-20B subunit is comprised of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 15-21, 23, 28, 29, 34 and 35.  
     
     
         2 . The soluble receptor of  claim 1  wherein the IL-22R subunit and the IL-20B subunit are linked together by a polypeptide linker.  
     
     
         3 . The soluble receptor of  claim 2  wherein the polypeptide linker has about 100 to 240 amino acid residues.  
     
     
         4 . The soluble receptor of  claim 3  wherein the polypeptide linker has about 170 amino acid residues.  
     
     
         5 . The soluble receptor of  claim 1  wherein the IL-22R subunit and the IL-20B subunit each have a polypeptide linker fused to the subunit, and each of the polypeptide linkers has at least one cysteine residue, wherein at least one disulfide bond forms with a cysteine from the polypeptide linker of the IL-22R subunit and with a cysteine from the polypeptide linker of the IL-20B subunit.  
     
     
         6 . The soluble receptor of  claim 5  wherein the IL-22R subunit is fused to all or a portion of the constant region of a heavy chain of an immunoglobulin (Ig) molecule, and the IL-20B subunit is fused to all or a portion of the constant region of a light chain of an immunoglobulin molecule, wherein the light chain and the heavy chain are disulfide bonded together.  
     
     
         7 . The soluble receptor of  claim 6  wherein the constant region of the heavy chain is comprised of a CH1 domain, a CH2 domain and a hinge sequence that connects the CH1 domain with the CH2 domain.  
     
     
         8 . The soluble receptor of  claim 6  wherein the IL-22R subunit fused to the constant region of the heavy chain is comprised of an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 26, 31 and 32, and the IL-20B subunit fused to the constant region of the light chain of the Ig molecule is comprised of an amino acid sequence selected from the group consisting of SEQ ID NOs: 28, 29, 34 and 35.  
     
     
         9 . The soluble receptor of  claim 5  wherein the IL-20B subunit is fused to all or a portion of the constant region of a heavy chain of an Ig molecule, and the IL-22R subunit is fused to all or a portion of the constant region of a light chain of an immunoglobulin molecule, wherein the light chain and the heavy chain are disulfide bonded together.  
     
     
         10 . A for producing a soluble receptor comprised of extracellular domains of IL-22R and IL-20RB comprising (a) introducing into a host cell a first DNA sequence comprised a DNA sequence that encodes the extracellular portion of IL-22R and the DNA that encodes an immunoglobulin light chain constant region;(b) introducing into the host cell a second DNA construct comprised of a DNA sequence that encodes the extracellular portion of IL-20RB and a DNA sequence that encodes an immunoglobulin heavy chain constant region domain; (c) growing the host cell in an appropriate growth medium under physiological conditions to allow production of a fusion protein comprised of the extracellular domain of IL-22R and IL-20RB; and (d) isolating the polypeptide from the host cell.  
     
     
         11 . A method for producing a soluble receptor comprised of the extracellular domains of IL-22R and IL-20RB comprising (a) introducing into a host cell a first DNA sequence comprised of DNA that encodes the extracellular portion of IL-20RB and the DNA that encodes an immunoglobulin light chain constant region;(b) introducing into the host cell a second DNA construct comprised of a DNA sequence that encodes the extracellular portion of IL-22R and a DNA sequence that encodes an immunoglobulin heavy chain constant region (c) growing the host cell in an appropriate growth medium under physiological conditions to allow the production of a dimerized heterodimeric fusion protein comprised of the extracellular domain of IL-22R and IL-20RB; and (d) isolating the dimerized polypeptide from the host cell.  
     
     
         12 . A method for producing a soluble receptor comprised of the extracellular domains of IL-22R and IL-20RB comprising (a) introducing into a host cell a DNA construct containing a DNA construct that encodes the extracellular portion of IL-20RB and a DNA construct of the extracellular portion of IL-22R, (b) growing the host cell in an appropriate medium under physiological conditions to allow the production of the extracellular domain of IL-22R and the extracellular domain of IL-20RB; and (d) isolating the polypeptides from the host cell.  
     
     
         13 . A host cells transformed or transfected with a DNA construct that encodes the extracellular domain of IL-22RB and a DNA construct that encodes the extracellular domain of IL-20RB.