Novel IFN receptor 1 binding proteins, DNA encoding them, and methods of modulating cellular response to interferons

Abstract

Novel proteins IR1B1 and IR1B4 have been isolated which bind to the type I IFN receptor IFNAR1 and function in the cellular response to IFNs. DNA encoding such proteins in either the sense or anti-sense orientation can be administered to either enhance or inhibit the cellular response to IFNs. Antibodies to the proteins can be used for isolation of the new protein or for immunodetection thereof.

What is claimed is:  
     
         1 . A method of prolonging tissue graft survival, comprising the steps of: 
 introducing into cells of a tissue or organ to be grafted to a patient in need thereof, an expression vector comprising a recombinant nucleic acid molecule comprising a DNA molecule, or a corresponding RNA molecule, comprising the nucleotide sequence SEQ ID NO:1 in the anti-sense orientation, or comprising the nucleotide sequence of a fragment of SEQ ID NO:1 in the anti-sense orientation, which fragment is of a size such that the transcription product of said nucleotide sequence hybridizes to sense mRNA encoding the interferon inducible IFNAR1 receptor binding protein of SEQ ID NO:2, to form a non-translatable double-stranded RNA molecule;    and grafting the tissue or organ to the patient.    
     
     
         2 . A method in accordance with  claim 1 , wherein said recombinant nucleic acid molecule comprises a recombinant DNA molecule further comprising a promoter operably linked to said anti-sense nucleotide sequence.  
     
     
         3 . A method in accordance with  claim 2 , wherein said nucleotide sequence of SEQ ID NO:1 or fragment thereof, when in the sense orientation, includes the initiation codon at the 5′-end of SEQ ID NO:1.  
     
     
         4 . A method of enhancing response to exogenous interferon therapy in treating cancer, comprising the steps of: 
 administering directly into a tumor a pharmaceutical composition comprising a pharmaceutically acceptable excipient and an expression vector comprising the recombinant DNA molecule comprising a nucleotide sequence encoding an IFN-α or IFN-β inducible IFNAR1 receptor binding protein, wherein the protein has the amino acid sequence of SEQ ID NO:2 operably linked to a promoter which is a constitutive promoter in human cells, such that said promoter promotes the transcription of said nucleotide sequence when the recombinant DNA molecule is in an appropriate expression host; and    subsequently administering exogenous interferon therapy.    
     
     
         5 . A method in accordance with  claim 4 , wherein said nucleotide sequence is SEQ ID NO:1.  
     
     
         6 . An IFNAR1-binding protein having the sequence of SEQ ID NO:2 or SEQ ID NO:8.  
     
     
         7 . A molecule comprising the antigen binding portion of an antibody specific for an IFNAR1-binding protein in accordance with  claim 6 .  
     
     
         8 . A molecule according to  claim 7 , consisting of a monoclonal antibody.