Human Receptor Proteins; Related Reagents and Methods

Abstract

Nucleic acids encoding mammalian, e.g., primate or rodent receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are provided.

1 . A composition of matter selected from:
 a) a substantially pure or recombinant DIRS1 polypeptide comprising at least three distinct nonoverlapping segments of at least four amino acids identical to segments of SEQ ID NO: 2;   b) a substantially pure or recombinant DIRS1 polypeptide comprising at least two distinct nonoverlapping segments of at least five amino acids identical to segments of SEQ ID NO: 2;   c) a natural sequence DIRS1 comprising mature SEQ ID NO: 2;   d) a fusion polypeptide comprising DIRS1 sequence;   e) a substantially pure or recombinant DIRS2 polypeptide comprising at least three distinct nonoverlapping segments of at least ten amino acids identical to segments of SEQ ID NO: 4;   f) a substantially pure or recombinant DIRS2 polypeptide comprising at least two distinct nonoverlapping segments of at least eleven amino acids identical to segments of SEQ ID NO: 4;   g) a natural sequence DIRS2 comprising SEQ ID NO: 4; or   h) a fusion polypeptide comprising DIRS2 sequence.   
     
     
         2 . The substantially pure or isolated antigenic:
 A) DIRS1 polypeptide of  claim 1 , wherein said distinct nonoverlapping segments of identity:
 a) include one of at least eight amino acids; 
 b) include one of at least four amino acids and a second of at least five amino acids; 
 c) include at least three segments of at least four, five, and six amino acids, or 
 d) include one of at least twelve amino acids; or 
   B) DIRS2 polypeptide of  claim 1 , wherein said distinct nonoverlapping segments of identity:
 a) include one of at least thirteen amino acids; 
 b) include one of at least eleven amino acids and a second of at least thirteen amino acids; 
 c) include at least three segments of at least ten, eleven, and twelve amino acids; or 
 d) include one of at least twenty-five amino acids. 
   
     
     
         3 . The composition of matter of  claim 1 , wherein said:
 a) DIRS1 polypeptide:
 i) comprises a mature sequence of Table 1; 
 ii) is an unglycosylated form of DIRS1; 
 iii) is from a primate, such as a human; 
 iv) comprises at least seventeen amino acids of SEQ ID NO: 2; 
 v) exhibits at least four nonoverlapping segments of at least seven amino acids of SEQ ID NO: 2; 
 vi) is a natural allelic variant of DIRS1; 
 vii) has a length at least about 30 amino acids; 
 viii) exhibits at least two non-overlapping epitopes which are specific for a primate DIRS1; 
 ix) is glycosylated; 
 x) has a molecular weight of at least 30 kD with natural glycosylation; 
 xi) is a synthetic polypeptide; 
 xii) is attached to a solid substrate; 
 xiii) is conjugated to another chemical moiety; 
 xiv) is a 5-fold or less substitution from natural sequence; or 
 xv) is a deletion or insertion variant from a natural sequence; or 
   b) DIRS2 polypeptide:
 i) comprises a mature sequence of Table 2; 
 ii) is an unglycosylated form of DIRS2; 
 iii) is from a primate, such as a human; 
 iv) comprises at thirty-five amino acids of SEQ ID NO: 4; 
 v) exhibits at least four nonoverlapping segments of at least twelve amino acids of SEQ ID NO: 4; 
 vi) is a natural allelic variant of DIRS2; 
 vii) has a length at least about 30 amino acids; 
 viii) exhibits at least two non-overlapping epitopes which are specific for a primate DIRS2; 
 ix) is glycosylated; 
 x) has a molecular weight of at least 30 kD with natural glycosylation; 
 xi) is a synthetic polypeptide; 
 xii) is attached to a solid substrate; 
 xiii) is conjugated to another chemical moiety; 
 xiv) is a 5-fold or less substitution from natural sequence; or 
 xv) is a deletion or insertion variant from a natural sequence. 
   
     
     
         4 . A composition comprising:
 a) a substantially pure DIRS1 and another Interferon Receptor family member;   b) a substantially pure DIRS2 and another Interferon Receptor family member;   c) a sterile DIRS1 polypeptide of  claim 1 ;   d) a sterile DIRS2 polypeptide of  claim 1 ;   e) said DIRS1 polypeptide of  claim 1  and a carrier, wherein said carrier is:
 i) an aqueous compound, including water, saline, and/or buffer; and/or 
 ii) formulated for oral, rectal, nasal, topical, or parenteral administration; or 
   f) said DIRS2 polypeptide of  claim 1  and a carrier, wherein said carrier is:
 i) an aqueous compound, including water, saline, and/or buffer; and/or 
 ii) formulated for oral, rectal, nasal, topical, or parenteral administration. 
   
     
     
         5 . The fusion polypeptide of  claim 1 , comprising:
 a) mature protein sequence of Table 1;   b) mature protein sequence of Table 2;   c) a detection or purification tag, including a FLAG, His 6, or Ig sequence; or   d) sequence of another interferon receptor protein.   
     
     
         6 . A kit comprising a polypeptide of  claim 1 , and:
 a) a compartment comprising said protein or polypeptide; or   b) instructions for use or disposal of reagents in said kit.   
     
     
         7 . A binding compound comprising an antigen binding site from an antibody, which specifically binds to a natural:
 A) DIRS1 polypeptide of  claim 1 , wherein:
 a) said binding compound is in a container; 
 b) said DIRS1 polypeptide is from a human; 
 c) said binding compound is an Fv, Fab, or Fab2 fragment; 
 d) said binding compound is conjugated to another chemical moiety; or 
 e) said antibody:
 i) is raised against a peptide sequence of a mature polypeptide of Table 1; 
 ii) is raised against a mature DIRS1; 
 iii) is raised to a purified human DIRS1; 
 iv) is immunoselected; 
 v) is a polyclonal antibody; 
 vi) binds to a denatured DIRS1; 
 vii) exhibits a Kd to antigen of at least 30 μM; 
 viii) is attached to a solid substrate, including a bead or plastic membrane; 
 ix) is in a sterile composition; or 
 x) is detectably labeled, including a radioactive or fluorescent label; or 
 
   B) DIRS2 polypeptide of  claim 1 , wherein:
 a) said binding compound is in a container; 
 b) said DIRS2 protein is from a human; 
 c) said binding compound is an Fv, Fab, or Fab2 fragment; 
 d) said binding compound is conjugated to another chemical moiety; or 
 e) said antibody:
 i) is raised against a peptide sequence of a mature polypeptide of Table 2; 
 ii) is raised against a mature DIRS2; 
 iii) is raised to a purified human DIRS2; 
 iv) is immunoselected; 
 v) is a polyclonal antibody; 
 vi) binds to a denatured DIRS2; 
 vii) exhibits a Kd to antigen of at least 30 μM; 
 viii) is attached to a solid substrate, including a bead or plastic membrane; 
 ix) is in a sterile composition; or 
 x) is detectably labeled, including a radioactive or fluorescent label. 
 
   
     
     
         8 . A kit comprising said binding compound of  claim 7 , and:
 a) a compartment comprising said binding compound; or   b) instructions for use or disposal of reagents in said kit.   
     
     
         9 . A method of producing an antigen:antibody complex, comprising contacting under appropriate conditions:
 a) a primate DIRS1 polypeptide with an antibody of  claim 7 A; or   b) a primate DIRS2 polypeptide with an antibody of  claim 7 B;   
       thereby allowing said complex to form. 
     
     
         10 . The method of  claim 9 , wherein:
 a) said complex is purified from other interferon receptors;   b) said complex is purified from other antibody;   c) said contacting is with a sample comprising an interferon;   d) said contacting allows quantitative detection of said antigen;   e) said contacting is with a sample comprising said antibody; or   f) said contacting allows quantitative detection of said antibody.   
     
     
         11 . A composition comprising:
 a) a sterile binding compound of  claim 7 ; or   b) said binding compound of  claim 7  and a carrier, wherein said carrier is:
 i) an aqueous compound, including water, saline, and/or buffer; and/or 
 ii) formulated for oral, rectal, nasal, topical, or parenteral administration. 
   
     
     
         12 . An isolated or recombinant nucleic acid encoding said:
 A) DIRS1 polypeptide of  claim 1 , wherein said:
 a) DIRS1 is from a human; or 
 b) said nucleic acid:
 i) encodes an antigenic peptide sequence of Table 1; 
 ii) encodes a plurality of antigenic peptide sequences of Table 1; 
 iii) exhibits identity over at least thirteen nucleotides to a natural cDNA encoding said segment; 
 iv) is an expression vector; 
 v) further comprises an origin of replication; 
 vi) is from a natural source; 
 vii) comprises a detectable label; 
 viii) comprises synthetic nucleotide sequence; 
 ix) is less than 6 kb, preferably less than 3 kb; 
 x) is from a primate; 
 xi) comprises a natural full length coding sequence; 
 xii) is a hybridization probe for a gene encoding said DIRS1; or 
 xiii) is a PCR primer, PCR product, or mutagenesis primer; or 
 
   B) DIRS2 polypeptide of  claim 1 , wherein said:
 a) DIRS2 is from a human; or 
 b) said nucleic acid:
 i) encodes an antigenic peptide sequence of Table 2; 
 ii) encodes a plurality of antigenic peptide sequences of Table 2; 
 iii) exhibits identity over at least 30 nucleotides to a natural cDNA encoding said segment; 
 iv) is an expression vector; 
 v) further comprises an origin of replication; 
 vi) is from a natural source; 
 vii) comprises a detectable label; 
 viii) comprises synthetic nucleotide sequence; 
 ix) is less than 6 kb, preferably less than 3 kb; 
 x) is from a primate; 
 xi) comprises a natural full length coding sequence; 
 xii) is a hybridization probe for a gene encoding said DIRS2; or 
 xiii) is a PCR primer, PCR product, or mutagenesis primer. 
 
   
     
     
         13 . A cell or tissue comprising said recombinant nucleic acid of  claim 12 . 
     
     
         14 . The cell of  claim 13 , wherein said cell is:
 a) a prokaryotic cell;   b) a eukaryotic cell;   c) a bacterial cell;   d) a yeast cell;   e) an insect cell;   f) a mammalian cell;   g) a mouse cell;   h) a primate cell; or   i) a human cell.   
     
     
         15 . A kit comprising said nucleic acid of  claim 12 , and:
 a) a compartment comprising said nucleic acid;   b) a compartment further comprising a primate DIRS1 polypeptide;   c) a compartment further comprising a primate DIRS2 polypeptide; or   d) instructions for use or disposal of reagents in said kit.   
     
     
         16 . A nucleic acid which:
 a) hybridizes under wash conditions of 30 minutes at 30° C. and less than 2M salt to the coding portion of SEQ ID NO: 1;   b) hybridizes under wash conditions of 30 minutes at 30° C. and less than 2M salt to the coding portion of SEQ ID NO: 3;   c) exhibits identity over a stretch of at least about 30 nucleotides to a primate DIRS1; or   d) exhibits identity over a stretch of at least about 30 nucleotides to a primate DIRS2.   
     
     
         17 . The nucleic acid of  claim 16 , wherein:
 a) said wash conditions are at 45° C. and/or 500 mM salt; or   b) said stretch is at least 55 nucleotides.   
     
     
         18 . The nucleic acid of  claim 16 , wherein:
 a) said wash conditions are at 55° C. and/or 150 mM salt; or   b) said stretch is at least 75 nucleotides.   
     
     
         19 . A method of modulating physiology or development of a cell or tissue culture cells comprising contacting said cell with an agonist or antagonist of a mammalian DIRS1 or DIRS2. 
     
     
         20 . The method of  claim 19 , wherein said cell is transformed with a nucleic acid encoding a DIRS1 or DIRS2 and another cytokine receptor subunit.