Interleukin-15 receptors

Abstract

There are disclosed Interleukin-15 Receptor (IL-15R) proteins, DNAs and expression vectors encoding IL-15R, and processes for producing IL-15R as products of recombinant cell cultures.

1 . An isolated DNA encoding an IL-15 receptor (IL-15R), wherein the DNA is selected from the group consisting of: 
 (a) a DNA having a nucleotide sequence as set forth in SEQ ID NO:1, nucleotides 91 through 789;    (b) a DNA having a nucleotide sequence as set forth in SEQ ID NO:6, nucleotides 34 through 753;    (c) DNAs that hybridize to the DNA sequences of (a) or (b) or their complementary strands under conditions of high stringency, and which encode polypeptides capable of binding IL-15; and    (d) DNAs that, due to degeneracy of the genetic code, encode polypeptides encoded by any of the foregoing DNAs.    
     
     
         2 . An isolated DNA according to  claim 1  that encodes a human IL-15R.  
     
     
         3 . An isolated DNA according to  claim 1  that encodes a soluble IL-15R.  
     
     
         4 . An isolated DNA according to  claim 3  wherein the DNA is selected from the group consisting of: 
 (a) a DNA having a nucleotide sequence as set forth in SEQ ID NO:1, nucleotides 91 through 612;    (b) a DNA having a nucleotide sequence as set forth in SEQ ID NO:6, nucleotides 34 through 567;    (c) a DNA that encodes a fragment of a peptide encoded by the sequences of (a) or (b), which fragment is capable of binding IL-15;    (d) DNAs that hybridize to the DNA sequences of (a), (b) or (c) or their complementary strands under conditions of high stringency, and which encode a polypeptide capable of binding IL-15; and    (e) DNAs that, due to degeneracy of the genetic code, encode a polypeptide encoded by any of the foregoing DNAs.    
     
     
         5 . An isolated DNA sequence according to  claim 3  that encodes a human IL-15R.  
     
     
         6 . An isolated DNA according to  claim 1 , encoding a modified IL-15R polypeptide having one or more changes in a primary amino acid sequence, which changes are selected from the group consisting of: inactivated N-linked glycosylation sites; modified KEX2 protease cleavage sites; deleted cysteine residues; and conservative amino acid substitutions, wherein the modified polypeptide binds IL-15.  
     
     
         7 . A recombinant expression vector comprising a DNA according to  claim 1 .  
     
     
         8 . A recombinant expression vector comprising a DNA according to  claim 4 .  
     
     
         9 . A recombinant expression vector comprising a DNA according to  claim 5 .  
     
     
         10 . A process for preparing an IL-15 receptor (IL-15R), comprising culturing a host cell transformed or transfected with a recombinant expression vector according to  claim 7  under conditions promoting expression, and recovering a polypeptide from the culture, wherein the polypeptide is capable of binding IL-15.  
     
     
         11 . A process for preparing an IL-15 receptor (IL-15R), comprising culturing a host cell transformed or transfected with a recombinant expression vector according to  claim 8  under conditions promoting expression, and recovering a polypeptide from the culture, wherein the polypeptide is capable of binding IL-15.  
     
     
         12 . A process for preparing an IL-15 receptor (IL-15R), comprising culturing a host cell transformed or transfected with a recombinant expression vector according to  claim 9  under conditions promoting expression, and recovering a polypeptide from the culture, wherein the polypeptide is capable of binding IL-15.  
     
     
         13 . An isolated IL-15 receptor (IL-15R) encoded by a DNA sequence according to  claim 1 .  
     
     
         14 . An IL-15 receptor (IL-15R) according to  claim 13  which is a soluble IL-15R.  
     
     
         15 . An IL-15 receptor (IL-15R) according to  claim 13 , comprising a polypeptide selected from the group consisting of: 
 (a) a polypeptide having an amino acid sequence as set forth in SEQ ID NO:2, having an amino terminus selected from the group consisting of amino acid 31, amino acid 34 and amino acid 35 of SEQ ID NO:2, and a carboxy terminus selected from the group consisting of amino acid 204 and amino acid 205 of SEQ ID NO:2;    (b) a polypeptide having an amino acid sequence as set forth in SEQ ID NO:6, having an amino terminus selected from the group consisting of amino acid 12, amino acid 15 and amino acid 16 of SEQ ID NO:6, and a carboxy terminus selected from the group consisting of an amino acid between amino acid 78 and amino acid 189 of SEQ ID NO:6; and    (c) a fragment of a polypeptide having an amino acid sequence of the polypeptide of (a) or (b), which fragment is capable of binding IL-15.    
     
     
         16 . Antibodies immunoreactive with mammalian IL-15 receptors.  
     
     
         17 . An antibody according to  claim 16  which is a monoclonal antibody.  
     
     
         18 . An antibody according to  claim 17  which is a blocking monoclonal antibody.