Novel tumor necrosis factor receptor homologs and nucleic acids encoding the same

Abstract

The present invention is directed to novel polypeptides having homology to members of the tumor necrosis factor receptor family and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

1 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding a DNA98853 polypeptide comprising the sequence of amino acid residues 1 to 299 of SEQ ID NO:3, or (b) the complement of the DNA molecule of (a). 
     
     
         2 . The nucleic acid of  claim 1 , wherein said DNA comprises the nucleotide sequence of SEQ ID NO:1 or its complement. 
     
     
         3 . The nucleic acid of  claim 1 , wherein said DNA comprises nucleotides 1-900 of the nucleotide sequence of SEQ ID NO:1. 
     
     
         4 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 203906 (DNA98853), or (b) the complement of the DNA molecule of (a). 
     
     
         5 . The nucleic acid of  claim 4  which comprises a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 203906 (DNA98853). 
     
     
         6 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding a DNA98853 polypeptide comprising the sequence of amino acid residues 1 to X of  FIG. 2  (SEQ ID NO:3), or (b) the complement of the DNA molecule of (a), wherein X is any one of amino acid residues 131-141 of  FIG. 2  (SEQ ID NO:3). 
     
     
         7 . An isolated nucleic acid comprising DNA from the group consisting of:
 a) a DNA having at least 80% sequence identity to a DNA sequence encoding a DNA98853 polypeptide comprising amino acid residues 1 to 299 of  FIG. 2  (SEQ ID NO:3);   b) a DNA sequence that hybridizes under stringent conditions to a DNA of a);   c) a DNA sequence that, due to the degeneracy of the genetic code, encodes a DNA98853 polypeptide of a); and   d) DNA complementary to the DNA of a), b), or c).   
     
     
         8 . A vector comprising the nucleic acid of  claim 1 . 
     
     
         9 . The vector of  claim 8  operably linked to control sequences recognized by a host cell transformed with the vector. 
     
     
         10 . A host cell comprising the vector of  claim 8 . 
     
     
         11 . The host cell of  claim 10 , wherein said cell is a CHO cell. 
     
     
         12 . The host cell of  claim 10 , wherein said cell is an  E. coli.    
     
     
         13 . The host cell of  claim 10 , wherein said cell is a yeast cell. 
     
     
         14 . A process for producing a DNA98853 polypeptide comprising culturing the host cell of  claim 10  under conditions suitable for expression of said DNA98853 polypeptide and recovering said DNA98853 polypeptide from the cell culture. 
     
     
         15 . An isolated DNA98853 polypeptide comprising amino acid residues 1 to 299 of  FIG. 2  (SEQ ID NO:3). 
     
     
         16 . An isolated DNA98853 polypeptide encoded by the cDNA insert of the vector deposited as ATCC Accession No. 203906 (DNA98853). 
     
     
         17 . An isolated DNA98853 polypeptide comprising amino acid residues 1 to X of  FIG. 2  (SEQ ID NO:3), wherein X is any one of amino acid residues 131-141  FIG. 2  (SEQ ID NO:3). 
     
     
         18 . An isolated DNA98853 polypeptide comprising a polypeptide selected from the group consisting of:
 a) a DNA98853 polypeptide comprising amino acid residues 1 to X of  FIG. 2  (SEQ ID NO:3), wherein X is any one of amino acid residues 131-141 of  FIG. 2  (SEQ ID NO:3); and   b) a fragment of a), wherein said fragment is a biologically active polypeptide.   
     
     
         19 . A chimeric molecule comprising a DNA98853 polypeptide fused to a heterologous amino acid sequence. 
     
     
         20 . The chimeric molecule of  claim 19 , wherein said heterologous amino acid sequence is an epitope tag sequence. 
     
     
         21 . The chimeric molecule of  claim 19 , wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin. 
     
     
         22 . An antibody which specifically binds to a DNA98853 polypeptide. 
     
     
         23 . The antibody of  claim 22 , wherein said antibody is a monoclonal antibody. 
     
     
         24 . A composition comprising an isolated DNA98853 polypeptide of  claim 15  and a carrier. 
     
     
         25 . The composition of  claim 24  wherein said carrier is a pharmaceutically-acceptable carrier. 
     
     
         26 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding a DNA101848 polypeptide comprising the sequence of amino acid residues 1 to 297 of  FIG. 4  (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a). 
     
     
         27 . The nucleic acid of  claim 26 , wherein said DNA comprises the nucleotide sequence of SEQ ID NO:4 or its complement. 
     
     
         28 . The nucleic acid of  claim 26 , wherein said DNA comprises nucleotides 1-894 of the nucleotide sequence of SEQ ID NO:4. 
     
     
         29 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 203907 (DNA101848), or (b) the complement of the DNA molecule of (a). 
     
     
         30 . The nucleic acid of  claim 29  which comprises a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 203907 (DNA101848). 
     
     
         31 . An isolated nucleic acid comprising DNA having at least 95% sequence identity to (a) a DNA molecule encoding a DNA101848 polypeptide comprising the sequence of amino acid residues 1 to X of  FIG. 4  (SEQ ID NO:6), or (b) the complement of the DNA molecule of (a), wherein X is any one of amino acid residues 131-141 of  FIG. 4  (SEQ ID NO:6). 
     
     
         32 . An isolated nucleic acid comprising DNA from the group consisting of:
 a) a DNA having at least 80% sequence identity to a DNA sequence encoding a DNA101848 polypeptide comprising amino acid residues 1 to 297 of  FIG. 4  (SEQ ID NO:6);   b) a DNA sequence that hybridizes under stringent conditions to a DNA of a);   c) a DNA sequence that, due to the degeneracy of the genetic code, encodes a DNA101848 polypeptide of a); and   d) DNA complementary to the DNA of a), b), or c).   
     
     
         33 . A vector comprising the nucleic acid of  claim 26 . 
     
     
         34 . The vector of  claim 33  operably linked to control sequences recognized by a host cell transformed with the vector. 
     
     
         35 . A host cell comprising the vector of  claim 33 . 
     
     
         36 . The host cell of  claim 35 , wherein said cell is a CHO cell. 
     
     
         37 . The host cell of  claim 35 , wherein said cell is an  E. coli.    
     
     
         38 . The host cell of  claim 35 , wherein said cell is a yeast cell. 
     
     
         39 . A process for producing a DNA101848 polypeptide comprising culturing the host cell of  claim 35  under conditions suitable for expression of said DNA101848 polypeptide and recovering said DNA101848 polypeptide from the cell culture. 
     
     
         40 . An isolated DNA101848 polypeptide comprising amino acid residues 1 to 297 of  FIG. 4  (SEQ ID NO:6). 
     
     
         41 . An isolated DNA101848 polypeptide encoded by the cDNA insert of the vector deposited as ATCC Accession No. 203907 (DNA101848). 
     
     
         42 . An isolated DNA101848 polypeptide comprising amino acid residues 1 to X of  FIG. 4  (SEQ ID NO:6), wherein X is any one of amino acid residues 131-141 of  FIG. 4  (SEQ ID NO:6). 
     
     
         43 . An isolated DNA101848 polypeptide comprising a polypeptide selected from the group consisting of:
 a) a DNA101848 polypeptide comprising amino acid residues 1 to X of  FIG. 4  (SEQ ID NO:6), wherein X is any one of amino acid residues 131-141 of  FIG. 4  (SEQ ID NO:6); and   b) a fragment of a), wherein said fragment is a biologically active polypeptide.   
     
     
         44 . A chimeric molecule comprising a DNA101848 polypeptide fused to a heterologous amino acid sequence. 
     
     
         45 . The chimeric molecule of  claim 44 , wherein said heterologous amino acid sequence is an epitope tag sequence. 
     
     
         46 . The chimeric molecule of  claim 44 , wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin. 
     
     
         47 . An antibody which specifically binds to a DNA101848 polypeptide. 
     
     
         48 . The antibody of  claim 47 , wherein said antibody is a monoclonal antibody. 
     
     
         49 . A composition comprising an isolated DNA101848 polypeptide of  claim 40  and a carrier. 
     
     
         50 . The composition of  claim 49  wherein said carrier is a pharmaceutically-acceptable carrier. 
     
     
         51 . A method of modulating apoptosis in mammalian cells, comprising exposing said cells to an effective amount of DNA98853 polypeptide or DNA101848 polypeptide. 
     
     
         52 . A method of modulating NF-KB activation in mammalian cells, comprising exposing said cells to an effective amount of DNA98853 polypeptide or DNA101848 polypeptide. 
     
     
         53 . A method of modulating a proinflammatory or autoimmune response in mammalian cells, comprising exposing said cells to an effective amount of DNA98853 polypeptide or DNA101848 polypeptide. 
     
     
         54 . A method of inhibiting or neutralizing EDA-A2 polypeptide biological activity in mammalian cells, comprising exposing said mammalian cells to an effective amount of EDA-A2 polypeptide antagonist. 
     
     
         55 . The method of  claim 54  wherein said EDA-A2 polypeptide antagonist comprises a DNA101848 or DNA98853 receptor immunoadhesin. 
     
     
         56 . The method of  claim 55  wherein said DNA101848 receptor immunoadhesin comprises a DNA101848 extracellular domain sequence fused to an Fc region of an immunoglobulin. 
     
     
         57 . The method of  claim 54  wherein said EDA-A2 polypeptide antagonist comprises a DNA101848 receptor linked to a nonproteinaceous polymer selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene. 
     
     
         58 . The method of  claim 54  wherein said EDA-A2 polypeptide antagonist comprises a DNA101848 receptor polypeptide or DNA98853 receptor polypeptide linked to a heterologous sequence. 
     
     
         59 . The method of  claim 58  wherein said heterologous sequence is an epitope tag sequence. 
     
     
         60 . The method of  claim 58  wherein said heterologous sequence is a leucine zipper sequence. 
     
     
         61 . The method of  claim 54  wherein said EDA-A2 polypeptide antagonist comprises an antibody selected from the group consisting of a DNA101848 receptor antibody and a DNA98853 receptor antibody.