Interleukin-20

Abstract

The present invention relates to a novel IL-20 protein which is a member of the cytokine polypeptide family. In particular, isolated nucleic acid molecules are provided encoding the human IL-20 protein. IL-20 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of IL-20 activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO: 2 (i.e., positions -20 to 160 of SEQ ID NO: 2);    (b) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO: 2 excepting the N-terminal methionine (i.e., positions −19 to 160 of SEQ ID NO: 2);    (c) a nucleotide sequence encoding the predicted mature IL-20 polypeptide having the amino acid sequence at positions 1 to 160 in SEQ ID NO: 2;    (d) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232;    (e) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209232;    (f) a nucleotide sequence encoding the mature IL-20 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No.209232; and    (g) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e) or (f), above.    
     
     
         2 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the complete nucleotide sequence in FIG. 1 (SEQ ID NO: 1).  
     
     
         3 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence in FIG. 1 (SEQ ID NO: 1) encoding the IL-20 polypeptide having the amino acid sequence in positions −19 to 160 of SEQ ID NO: 2.  
     
     
         4 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence in FIG. 1 (SEQ ID NO: 1) encoding the mature IL-20 polypeptide having the amino acid sequence from about 1 to about 160 in SEQ ID NO: 2.  
     
     
         5 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues n 2 −160 of SEQ ID NO: 2, where n 2  is an integer in the range of −20 to 10;    (b) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues −20-m 2  of SEQ ID NO: 2, where mi is an integer in the range of 158 to 160;    (c) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n 2 -m 2  of SEQ ID NO: 2, where n 2  and m 2  are integers as defined respectively in (a) and (b) above; and    (d) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete IL-20 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232 wherein said portion excludes from 1 to about 30 amino acids from the amino terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232;    (e) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete IL-20 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232 wherein said portion excludes from 1 to about 3 amino acids from the carboxy terminus of said complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232; and    (f) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete IL-20 amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232 wherein said portion include a combination of any of the amino terminal and carboxy terminal deletions in (d) and (e), above.    
     
     
         6 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the complete nucleotide sequence of the cDNA clone contained in ATCC Deposit No. 209232.  
     
     
         7 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209232.  
     
     
         8 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence encoding the mature IL-20 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232.  
     
     
         9 . An isolated nucleic acid molecule comprising a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide having a nucleotide sequence identical to a nucleotide sequence in (a), (b), (c), (d), (e), (f) or (g) of  claim 1  wherein said polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues.  
     
     
         10 . An isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of an IL-20 polypeptide having an amino acid sequence in (a), (b), (c), (d), (e) or (f) of  claim 1 .  
     
     
         11 . The isolated nucleic acid molecule of  claim 10 , which encodes an epitope-bearing portion of an IL-20 polypeptide wherein the amino acid sequence of said portion is selected from the group of sequences in SEQ ID NO: 2 consisting of: about Gln-21 to about Arg-29, about Gln-21 to about Gly-41, about Ser-24 to about Gln-32, about Arg-29 to about Pro-37, about Arg-52 to about Glu-60, about Arg-52 to about Met-69, about Glu-61 to about Met-69, about Asn-75 to about Val-86, about Ser-93 to about Trp-101, about Ile-105 to about Pro-113, about Met-132 to about Ser-140, about Arg-150 to about Pro-158, about Pro-156 to about Arg-164, about Gly-161 to about Met-169, and about Val-149 to about Ala-167.  
     
     
         12 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         13 . A recombinant vector produced by the method of  claim 12 .  
     
     
         14 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 13  into a host cell.  
     
     
         15 . A recombinant host cell produced by the method of  claim 14 .  
     
     
         16 . A recombinant method for producing an IL-20 polypeptide, comprising culturing the recombinant host cell of  claim 15  under conditions such that said polypeptide is expressed and recovering said polypeptide.  
     
     
         17 . An isolated IL-20 polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO: 2 (i.e., positions −20 to 160 of SEQ ID NO: 2);    (b) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO: 2 excepting the N-terminal methionine (i.e., positions −19 to 160 of SEQ ID NO: 2);    (c) the amino acid sequence of the predicted mature IL-20 polypeptide having the amino acid sequence at positions 1 to 160 in SEQ ID NO: 2;    (d) the complete amino acid sequence encoded by the cDNA clone contained in the ATCC Deposit No. 209232;    (e) the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in the ATCC Deposit No. 209232; and    (f) the complete amino acid sequence of the predicted mature IL-20 polypeptide encoded by the cDNA clone contained in the ATCC Deposit No. 209232.    
     
     
         18 . An isolated polypeptide comprising an epitope-bearing portion of the IL-20 protein, wherein said portion is selected from the group consisting of: a polypeptide comprising amino acid residues from about Gln-21 to about Arg-29 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Gln-21 to about Gly-41 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Ser-24 to about Gln-32 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Arg-29 to about Pro-37 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Arg-52 to about Glu-60 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Arg-52 to about Met-69 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Glu-61 to about Met-69 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Asn-75 to about Val-86 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Ser-93 to about Trp-101 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Ile-105 to about Pro-113 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Met-1 32 to about Ser-140 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Arg-150 to about Pro-158 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Pro-156 to about Arg-164 in SEQ ID NO: 2, a polypeptide comprising amino acid residues from about Gly-161 to about Met-169 in SEQ ID NO: 2, and a polypeptide comprising amino acid residues from about Val-149 to about Ala-1 67 in SEQ ID NO: 2.  
     
     
         19 . An isolated antibody that binds specifically to an IL-20 polypeptide of  claim 17.