Dendritic cell-derived growth factor

Abstract

The present invention relates to a novel DCDGF protein which is a member of a novel family of growth factors of which the prototype is called Insect-Derived Growth Factor (IDGF). In particular, isolated nucleic acid molecules are provided encoding the human DCDGF protein. DCDGF 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 DCDGF activity. Also provided are diagnostic methods for diagnosing DiGeorge Syndrome and, particularly, immune system-related disorders. and therapeutic methods for treating immune system-related disorders.

What is claimed is:  
     
         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 the full-length DCDGF polypeptide having the complete amino acid sequence in FIGS.  1 A- 1 C (SEQ ID NO:2);    (b) a nucleotide sequence encoding the DCDGF polypeptide having the complete amino acid sequence in FIGS.  1 A- 1 C excepting the N-terminal methionine (i.e., positions −25 to 485 in SEQ ID NO:2):    (c) a nucleotide sequence encoding the mature DCDGF polypeptide having the amino acid sequence at positions 27 to 511 in FIGS.  1 A- 1 C (positions 1 to 485 in SEQ ID NO:2);    (d) a nucleotide sequence encoding the full-length DCDGF polypeptide having the complete amino acid sequence encoded by the human cDNA contained in ATCC Deposit No. 97852;    (e) a nucleotide sequence encoding the full-length DCDGF polypeptide excepting the N-terminal methionine encoded by the human cDNA contained in ATCC Deposit No. 97852;    (f) a nucleotide sequence encoding the mature DCDGF polypeptide encoded by the human cDNA contained in ATCC Deposit No. 97852; 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 FIGS.  1 A- 1 C (SEQ ID NO:1).  
     
     
         3 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence in FIGS.  1 A- 1 C (SEQ ID NO:1) encoding the DCDGF polypeptide having the complete amino acid sequence in SEQ ID NO:2.  
     
     
         4 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence in FIGS.  1 A- 1 C (SEQ ID NO:1) encoding the mature DCDGF polypeptide having the amino acid sequence from about position 1 to about 485 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-485 of SEQ ID NO:2, where n is any integer except zero in the range of about −25 to about +19;    (b) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of residues −25 to m of SEQ ID NO:2, where m is any integer except zero in the range of 464 to 484;    (c) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-m of SEQ ID NO:2, where n and m are integers as defined respectively in (a) and (b) above;    (d) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete DCDGF amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97852 wherein said portion excludes from 1 to about 45 amino acids from the amino terminus of said complete amino acid sequence;    (e) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete DCDGF amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97852 wherein said portion excludes from 1 to about 20 amino acids from the carboxy terminus of said complete amino acid sequence; and    (f) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete DCDGF amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97852 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 human cDNA contained in ATCC Deposit No. 97852.  
     
     
         7 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence encoding the DCDGF polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the human cDNA contained in ATCC Deposit No. 97852.  
     
     
         8 . The nucleic acid molecule of  claim 1  wherein said polynucleotide has the nucleotide sequence encoding the mature DCDGF polypeptide having the amino acid sequence encoded by the human cDNA contained in ATCC Deposit No. 97852.  
     
     
         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 a DCDGF 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 comprises a sequence encoding an epitope-bearing portion of a DCDGF polypeptide wherein the amino acid sequence of said portion is selected from the group of sequences in SEQ ID NO:2 consisting of: about Leu −25 to about Ala −16; about His 124 to about Lys 135; about Leu 139 to about Val 149, about Gly 332 to about Leu 346; about Tyr 371 to about Ile 379, and about Ile 412 to about Met 419.  
     
     
         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 a DCDGF 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 DCDGF polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) the complete amino acid sequence shown in FIGS.  1 A- 1 C (residues −26 to 485 in SEQ ID NO:2);    (b) the amino acid sequence shown as positions 2 to 511 in FIGS.  1 A- 1 C (residues −25 to 485 of SEQ ID NO:2);    (c) the amino acid sequence shown as positions 26 to 511 in FIGS.  1 A- 1 C (residues 1 to 485 in SEQ ID NO:2);    (d) the complete amino acid sequence encoded by the human cDNA contained in ATCC Deposit No. 97852;    (e) the complete amino acid sequence excepting the N-terminal methionine encoded by the human cDNA contained in ATCC Deposit No. 97852; and    (f) the mature polypeptide encoded by the human cDNA contained in ATCC Deposit No. 97852.    
     
     
         18 . An isolated polypeptide comprising an epitope-bearing portion of the DCDGF protein, wherein the amino acid sequence of said portion is selected from the group of sequences in SEQ ID NO:2 consisting of: about Leu −25 to about Ala −16; about His 124 to about Lys 135; about Leu 139 to about Val 149, about Gly 332 to about Leu 346; about Tyr 371 to about Ile 379, and about Ile 412 to about Met 419.  
     
     
         19 . An isolated antibody that binds specifically to a DCDGF polypeptide of  claim 17 .  
     
     
         20 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence of at least 30 contiguous nucleotides of SEQ ID NO:1.  
     
     
         21 . A isolated nucleic acid molecule having a nucleotide sequence complimentary to the nucleic acid molecule of  claim 20.