Il-1 related polypeptides

Abstract

The present invention is directed to novel polypeptides having homology to the IL-1-like family of proteins 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 methods for producing the polypeptides of the present invention.

1 . An isolated DNA molecule selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra1 polypeptide comprising the amino acid sequence of amino acid residues from about 37 to about 203 of  FIG. 2  (SEQ ID NO:5); (2) a DNA molecule encoding an hIL-1Ra1 polypeptide comprising the amino acid sequence of amino acid residues from about 15 to about 193 of  FIG. 3  (SEQ ID NO:7); (3) a DNA molecule encoding an hIL-1Ra2 polypeptide comprising the amino acid sequence of amino acid residues from about 1 to about 134 of  FIG. 5  (SEQ ID NO:10); (4) a DNA molecule encoding an hIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 95 to about 134 of  FIG. 7  (SEQ ID NO:13); (5) a DNA molecule encoding a mIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 95 to about 134 of  FIG. 9  (SEQ ID NO:16); (6) a DNA molecule encoding an hIL-1Ra1L polypeptide comprising the amino acid sequence of amino acid residues from about 26 to about 207 of  FIG. 15  (SEQ ID NO:19); (7) a DNA molecule encoding an hIL-1Ra1S polypeptide comprising the amino acid sequence of amino acid residues from about 26 to about 167 of  FIG. 16  (SEQ ID NO:21); (8) a DNA molecule encoding an hIL-1Ra1V polypeptide comprising the amino acid sequence of amino acid residues from about 46 to about 218 of  FIG. 19  (SEQ ID NO:25); and (9) the complement of any of the DNA molecules of (1)-(8).  
     
     
         2 . The isolated DNA molecule of  claim 1  selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra1 polypeptide comprising the amino acid sequence of amino acid residues from about 37 to about 203 of  FIG. 2  (SEQ ID NO:5); (2) a DNA molecule encoding an hIL-1Ra1 polypeptide comprising the amino acid sequence of amino acid residues from about 15 to about 193 of  FIG. 3  (SEQ ID NO:7); (3) a DNA molecule encoding an hIL-1Ra2 polypeptide comprising the amino acid sequence of amino acid residues from about 1 to about 134 of  FIG. 5  (SEQ ID NO:10); (4) a DNA molecule encoding an hIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 95 to about 134 of  FIG. 7  (SEQ ID NO:13); (5) a DNA molecule encoding a mIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 95 to about 134 of  FIG. 9  (SEQ ID NO:16); and (6) the complement of any of the DNA molecules of (1)-(5).  
     
     
         3 . The isolated DNA molecule of  claim 1  selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra1L polypeptide comprising the amino acid sequence of amino acid residues from about 26 to about 207 of  FIG. 15  (SEQ ID NO:19); (2) a DNA molecule encoding an hIL-1Ra1S polypeptide comprising the amino acid sequence of amino acid residues from about 26 to about 167 of  FIG. 16  (SEQ ID NO:21); (3) a DNA molecule encoding an hIL-1Ra1V polypeptide comprising the amino acid sequence of amino acid residues from about 46 to about 218 of  FIG. 19  (SEQ ID NO:25); and (4) the complement of any of the DNA molecules of (1)-(3).  
     
     
         4 . The isolated DNA molecule of  claim 3  selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra1L polypeptide comprising the amino acid sequence of amino acid residues from about 1 to about 207 of  FIG. 15  (SEQ ID NO:19); (2) a DNA molecule encoding an hIL-1Ra1S polypeptide comprising the amino acid sequence of amino acid residues from about 1 to about 167 of  FIG. 16  (SEQ ID NO:21); (3) a DNA molecule encoding an hIL-1Ra1V polypeptide comprising the amino acid sequence of amino acid residues from about 1 to about 218 of  FIG. 19  (SEQ ID NO:25); and (4) the complement of any of the DNA molecules of (1)-(2).  
     
     
         5 . The isolated DNA molecule of  claim 2  selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 34 to about 155 of  FIG. 7  (SEQ ID NO:13); (2) a DNA molecule encoding a mIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 34 to about 155 of  FIG. 9  (SEQ ID NO:16); and (3) the complement of any of the DNA molecules of (1)-(2).  
     
     
         6 . The isolated DNA molecule of  claim 5  selected from the group consisting of: (1) a DNA molecule encoding an hIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 2 to about 155 of  FIG. 7  (SEQ ID NO:13); (2) a DNA molecule encoding a mIL-1Ra3 polypeptide comprising the amino acid sequence of amino acid residues from about 2 to about 155 of  FIG. 9  (SEQ ID NO:16); and (3) the complement of any of the DNA molecules of (1)-(2).  
     
     
         7 . The isolated DNA molecule of  claim 1  selected from the group consisting of: (1) a DNA molecule which encodes an hIL-1Ra1 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 118 to about 618 in the sense strand of  FIG. 2  (SEQ ID NO:4); (2) a DNA molecule which encodes an hIL-1Ra1 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 145 to about 681 in the sense strand of  FIG. 3  (SEQ ID NO:6); (3) a DNA molecule which encodes an hIL-1Ra2 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 96 to about 497 in the sense strand of  FIG. 5  (SEQ ID NO:9); (4) a DNA molecule which encodes an hIL-1Ra3 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 283 to about 402 in the sense strand of  FIG. 7  (SEQ ID NO:12); (5) a DNA molecule which encodes a mIL-1Ra3 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 427 to about 546 in the sense strand of  FIG. 9  (SEQ ID NO:15); (6) a DNA molecule which encodes an hIL-1Ra1L polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 79 to about 624 in the sense strand of  FIG. 15  (SEQ ID NO:18); (7) a DNA molecule which encodes an hIL-1Ra1S polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 79 to about 504 in the sense strand of  FIG. 16  (SEQ ID NO:20); (8) a DNA molecule which encodes an hIL-1Ra1V polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 208 to about 726 in the sense strand of  FIG. 19  (SEQ ID NO:24); and (9) the complement of any of the DNA molecules of (1)-(8).  
     
     
         8 . The isolated DNA molecule of  claim 7  selected from the group consisting of: (1) a DNA molecule which encodes an hIL-1Ra1 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 118 to about 618 in the sense strand of  FIG. 2  (SEQ ID NO:4); (2) a DNA molecule which encodes an hIL-1Ra1 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 145 to about 681 in the sense strand of  FIG. 3  (SEQ ID NO:6); (3) a DNA molecule which encodes an hIL-1Ra2 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 96 to about 497 in the sense strand of  FIG. 5  (SEQ ID NO:9); (4) a DNA molecule which encodes an hIL-1Ra3 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 283 to about 402 in the sense strand of  FIG. 7  (SEQ ID NO:12); (5) a DNA molecule which encodes a mIL-1Ra3 polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 427 to about 546 in the sense strand of  FIG. 9  (SEQ ID NO:15); and (6) the complement of any of the DNA molecules of (1)-(5).  
     
     
         9 . The isolated DNA molecule of  claim 7  selected from the group consisting of: (1) a DNA molecule which encodes an hIL-1Ra1L polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 79 to about 624 in the sense strand of  FIG. 15  (SEQ ID NO:18); (2) a DNA molecule which encodes an hIL-1Ra1S polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 79 to about 504 in the sense strand of  FIG. 16  (SEQ ID NO:20); (3) a DNA molecule which encodes an hIL-1Ra1V polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 208 to about 726 in the sense strand of  FIG. 19  (SEQ ID NO:24); and (4) the complement of any of the DNA molecules of (1)-(3).  
     
     
         10 . The isolated DNA molecule of  claim 9  selected from the group consisting of: (1) a DNA molecule which encodes an hIL-1Ra1L polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 4 to about 624 in the sense strand of  FIG. 15  (SEQ ID NO:18); (2) a DNA molecule which encodes an hIL-1Ra1S polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 4 to about 504 in the sense strand of  FIG. 16  (SEQ ID NO:20); (3) a DNA molecule which encodes an hIL-1Ra1V polypeptide, and which comprises the nucleic acid sequence of nucleotide positions from about 73 to about 726 in the sense strand of  FIG. 19  (SEQ ID NO:24); and (4) the complement of any of the DNA molecules of (1)-(3).  
     
     
         11 . The isolated nucleic acid molecule of  claim 8  selected from the group consisting of: (1) a DNA molecule comprising the nucleic acid sequence of nucleotide positions from about 103 to about 681 in the sense strand of  FIG. 3  (SEQ ID NO:6); (2) a DNA molecule comprising the nucleic acid sequence of nucleotide positions from about 100 to about 465 in the sense strand of  FIG. 7  (SEQ ID NO:12); (3) a DNA molecule comprising the nucleic acid sequence of nucleotide positions from about 244 to about 609 in the sense strand of  FIG. 9  (SEQ ID NO:15); and (4) the complement of any of the DNA molecules of (1)-(3).  
     
     
         12 . The isolated nucleic acid molecule of  claim 8  comprising (a) the complete DNA sequence in the sense strand of  FIG. 2  (SEQ ID NO:4),  FIG. 3  (SEQ ID NO:6),  FIG. 5  (SEQ ID NO:9),  FIG. 7  (SEQ ID NO:12), or  FIG. 9  (SEQ ID NO:15), or (b) the complement of (a).  
     
     
         13 . An isolated nucleic acid molecule encoding an IL-1lp polypeptide, comprising DNA hybridizing to the complement of a nucleic acid sequence selected from the group consisting of: (1) the nucleic acid sequence consisting of nucleotide positions from about 238 to about 465 in the sense strand of  FIG. 7  (SEQ ID NO:12); (2) the nucleic acid sequence consisting of nucleotide positions from about 427 to about 609 in the sense strand of  FIG. 9  (SEQ ID NO:15); and (3) the nucleic acid sequence consisting of nucleotide positions from about 114 to about 135 in the sense strand of  FIG. 15  (SEQ ID NO:18).  
     
     
         14 . An isolated nucleic acid molecule comprising (a) a DNA molecule encoding a polypeptide selected from the group consisting of: (1) a polypeptide comprising the entire amino acid sequence encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203588; (2) a polypeptide comprising the entire amino acid sequence, or the entire amino acid sequence excluding the 36 N-terminal amino acid residues of such sequence, encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203587; (3) a polypeptide comprising the entire amino acid sequence encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203586; (4) a polypeptide comprising the entire amino acid sequence, or the entire amino acid sequence excluding the N-terminal amino acid residue of such sequence, encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203589; (5) a polypeptide comprising the entire amino acid sequence, or the entire amino acid sequence excluding the N-terminal amino acid residue of such sequence, encoded by the cDNA insert in the vector deposited as ATCC Deposit No. 203590; (6) a polypeptide comprising the entire amino acid sequence, or the entire amino acid sequence excluding the 34 N-terminal amino acid residues of such sequence, encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203846; (7) a polypeptide comprising the entire amino acid sequence encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203855; and (8) a polypeptide comprising the entire amino acid sequence, or the entire amino acid sequence excluding the 45 N-terminal amino acid residues of such sequence, encoded by the longest open reading frame in the cDNA insert in the vector deposited as ATCC Deposit No. 203973; or (b) the complement of the DNA molecule of (a).  
     
     
         15 . An isolated nucleic acid molecule comprising (a) DNA encoding the IL-1lp polypeptide of  claim 21 , or (b) the complement of the DNA of (a).  
     
     
         16 . A vector comprising the nucleic acid of  claim 1 .  
     
     
         17 . The vector of  claim 16  operably linked to control sequences recognized by a host cell transfected with the vector.  
     
     
         18 . A host cell comprising the vector of  claim 16 .  
     
     
         19 . A process for producing an IL-1lp polypeptide comprising the steps of: (1) culturing a host cell comprising the DNA molecule of  claim 15  under conditions suitable for expression of the IL-1lp polypeptide encoded by the DNA molecule; and (2) recovering said IL-1lp polypeptide from the cell culture.  
     
     
         20 . An isolated IL-1lp polypeptide encoded by the nucleic acid molecule of  claim 1 .  
     
     
         21 . An isolated IL-1lp polypeptide selected from the group consisting of: (1) an hIL-1Ra1V polypeptide consisting of an amino acid sequence having at least an 80% sequence identity to the sequence of amino acid residues from about 46 to about 218 of  FIG. 19  (SEQ ID NO:25); (2) an hIL-1Ra3 polypeptide consisting of an amino acid sequence having at least an 80% sequence identity to the sequence of amino acid residues from about 95 to about 134 of  FIG. 7  (SEQ ID NO:13); and (3) a mIL-1Ra3 polypeptide consisting of an amino acid sequence having at least an 80% sequence identity to the sequence of amino acid residues from about 95 to about 134 of  FIG. 9  (SEQ ID NO:16).  
     
     
         22 . An isolated IL-1lp polypeptide selected from the group consisting of: (1) an hIL-1Ra1 polypeptide comprising amino acid residues from about 37 to about 203 of  FIG. 2  (SEQ ID NO:5); (2) an hIL-1Ra1 polypeptide comprising amino acid residues from about 15 to about 193 of  FIG. 3  (SEQ ID NO:7); (3) an hIL-1Ra2 polypeptide comprising amino acid residues from about 1 to about 134 of  FIG. 5  (SEQ ID NO:10); (4) an hIL-1Ra3 polypeptide comprising amino acid residues from about 95 to about 134 of  FIG. 7  (SEQ ID NO:13); (5) a mIL-1Ra3 polypeptide comprising amino acid residues from about 95 to about 134 of  FIG. 9  (SEQ ID NO:16); (6) an hIL-1Ra1L polypeptide comprising amino acid residues from about 26 to about 207 of  FIG. 15  (SEQ ID NO:19); (7) an hIL-1Ra1S polypeptide comprising amino acid residues from about 26 to about 167 of  FIG. 16  (SEQ ID NO:21); and (8) an hIL-1Ra1V polypeptide comprising amino acid residues from about 46 to about 218 of  FIG. 19  (SEQ ID NO:25).  
     
     
         23 . The isolated IL-1lp polypeptide of  claim 22  selected from the group consisting of: (1) an hIL-1Ra1L polypeptide comprising amino acid residues from about 1 to about 207 of  FIG. 15  (SEQ ID NO:19); (2) an hIL-1Ra1S polypeptide comprising amino acid residues from about 1 to about 167 of  FIG. 16  (SEQ ID NO:21); and (3) an hIL-1Ra1V polypeptide comprising amino acid residues from about 1 to about 218 of  FIG. 19  (SEQ ID NO:25).  
     
     
         24 . The isolated polypeptide of  claim 22  selected from the group consisting of: (1) an hIL-1Ra3 polypeptide comprising amino acid residues from about 34 to about 155 of  FIG. 7  (SEQ ID NO:13); and (2) a mIL-1Ra3 polypeptide comprising amino acid residues from about 34 to about 155 of  FIG. 9  (SEQ ID NO:16).  
     
     
         25 . The polypeptide encoded by the DNA molecule of (a) in  claim 14 .  
     
     
         26 . The IL-1lp polypeptide of  claim 22  that comprises a native amino acid sequence of the IL-1lp fused at its C-terminus or N-terminus to a heterologous amino acid sequence.  
     
     
         27 . The IL-1lp polypeptide of  claim 26 , wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         28 . The IL-1lp polypeptide of  claim 26 , wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin.  
     
     
         29 . An antibody which specifically binds to the IL-1lp polypeptide of  claim 22 .  
     
     
         30 . The antibody of  claim 29 , wherein said antibody is a monoclonal antibody.