Interleukin-19

Abstract

The present invention concerns a novel human cytokine. In particular, isolated nucleic acid molecules are provided encoding interleukin-19 (IL-19). IL-19 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The IL-19 polypeptides of the present invention can also be used to raise polyclonal and monoclonal antibodies. The invention further concerns therapeutic methods for modulating cytokine production.

1 . 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 amino acids from about −24 to about 153 in SEQ ID NO:2;    (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about −23 to about 153 in SEQ ID NO:2;    (c) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 153 in SEQ ID NO:2;    (d) a nucleotide sequence encoding a polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662;    (e) a nucleotide sequence encoding the mature IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662; and    (f) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d) or (e).    
     
     
         2 . 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) or (e) 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.  
     
     
         3 . An isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of a IL-19 polypeptide having an amino acid sequence in (a), (b), (c), (d), or (e) of  claim 1 .  
     
     
         4 . The isolated nucleic acid molecule of  claim 3 , which encodes an epitope-bearing portion of a IL-19 polypeptide comprising amino acid residues from about −5 to about 4 in SEQ ID NO:2.  
     
     
         5 . An isolated nucleic acid molecule, comprising a polynucleotide having a sequence selected from the group consisting of the nucleotide sequence of a fragment of the sequence shown in SEQ ID NO: 1 or the complement thereof, wherein said fragment comprises at least 50 contiguous nucleotides of SEQ ID NO: 1, provided that said fragment does not have a sequence starting: 
 (a) at nucleotide 9 and ending at nucleotide 302 of SEQ ID NO:1 or any subfragment thereof or the complement thereof; or    (b) at nucleotide 438 and ending at nucleotide 934 of SEQ ID NO:1 or any subfragment thereof or the complement thereof.    
     
     
         6 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         7 . A recombinant vector produced by the method of  claim 6 .  
     
     
         8 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 7  into a host cell.  
     
     
         9 . A recombinant host cell produced by the method of  claim 8 .  
     
     
         10 . A recombinant method for producing a IL-19 polypeptide, comprising culturing the recombinant host cell of  claim 9  under conditions such that said polypeptide is expressed and recovering said polypeptide.  
     
     
         11 . An isolated IL-19 polypeptide having an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) amino acids from about −24 to about 153 in SEQ ID NO:2;    (b) amino acids from about −23 to about 153 in SEQ ID NO:2;    (c) amino acids from about 1 to about 153 in SEQ ID NO:2;    (d) the amino acid sequence of the IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662;    (e) the amino acid sequence of the mature IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662; and    (f) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d) or (e).    
     
     
         12 . An isolated polypeptide comprising an epitope-bearing portion of the IL-19 protein, wherein said portion is selected from the group consisting of: a polypeptide comprising amino acid residues from about −5 to about 4 in SEQ ID NO:2; a polypeptide comprising amino acid residues from about 64 to about 82 in SEQ ID NO:2; and a polypeptide comprising amino acid residues from about 115 to about 125 in SEQ ID NO:2.  
     
     
         13 . The isolated polypeptide of  claim 11 , which is produced or contained in a recombinant host cell.  
     
     
         14 . The isolated polypeptide of  claim 11 , wherein said recombinant host cell is mammalian.  
     
     
         15 . An isolated nucleic acid molecule comprising a polynucleotide encoding an IL-19 polypeptide wherein, except for at least one to fifty conservative amino acid substitution, said polypeptide has a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide comprising amino acids from about −24 to about 153 in SEQ ID NO:2;    (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about −23 to about 153 in SEQ ID NO:2;    (c) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 153 in SEQ ID NO:2;    (d) a nucleotide sequence encoding a polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662;    (e) a nucleotide sequence encoding the mature IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662; and    (f) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d) or (e).    
     
     
         16 . An isolated IL-19 polypeptide wherein, except for at least one to fifty conservative amino acid substitution, said polypeptide has a sequence selected from the group consisting of: 
 (a) amino acids from about −24 to about 153 in SEQ ID NO:2;    (b) amino acids from about −23 to about 153 in SEQ ID NO:2;    (c) amino acids from about 1 to about 153 in SEQ ID NO:2;    (d) the amino acid sequence of the IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662;    (e) the amino acid sequence of the mature IL-19 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97662; and    (f) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d) or (e).    
     
     
         17 . A method for treatment of an individual in need of a decreased level of IFN-γ, TNF-α, or IL-6 activity comprising administering to said individual a composition comprising an isolated polypeptide of  claim 16 .  
     
     
         18 . A method for treatment of an individual in need of an increase in IL-2 activity, comprising administering to said individual a composition comprising an antagonist of interleukin-19 activity.