Isolated mammalian monocyte cell genes; related reagents

Abstract

Nucleic acids encoding various monocyte cell proteins from a primate, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

1 . A composition of matter selected from the group consisting of:
 a) a substantially pure or recombinant FDF03 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to a mature polypeptide from SEQ ID NO:2 or 4;   b) a natural sequence FDF03 of SEQ ID NO:2 or 4;   c) a fusion protein comprising FDF03 sequence;   d) a substantially pure or recombinant YE01 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to a mature polypeptide from SEQ ID NO:6, 8, or 10;   e) a natural sequence YE01 of SEQ ID NO:6, 8, or 10;   f) a fusion protein comprising YE01 sequence;   g) a substantially pure or recombinant KTE03 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to SEQ ID NO:12, 14, 16, 18, 20, or 22;   h) a natural sequence KTE03 of SEQ ID NO:12, 14, 16, 18, 20, or 22; and   i) a fusion protein comprising KTE03 sequence.   
     
     
         2 . A substantially pure or isolated protein comprising a segment exhibiting sequence identity to a corresponding portion of a FDF03, YE01, or KTE03 of  claim 1 , wherein:
 a) said homology is at least about 90% identity and said portion is at least about 9 amino acids;   b) said homology is at least about 80% identity and said portion is at least about 17 amino acids; or   c) said homology is at least about 70% identity and said portion is at least about 25 amino acids.   
     
     
         3 . The composition of matter of  claim 1 , wherein said:
 a) FDF03 comprises a mature sequence of Table 1;   b) YE01 comprises a mature sequence of Table 2;   c) KTE03 comprises a mature sequence of Table 3;   d) protein or peptide: i) is from a warm blooded animal selected from a mammal, including a primate or rodent;
 ii) comprises at least one polypeptide segment of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, or 22; 
 iii) exhibits a plurality of portions exhibiting said identity; 
 iv) is a natural allelic variant of FDF03, YE01, or KTE03; 
 v) has a length at least about 30 amino acids; 
 vi) exhibits at least two non-overlapping epitopes which are specific for a mammalian FDF03, YE01, or KTE03; 
 vii) exhibits a sequence identity at least about 90% over a length of at least about 20 amino acids to a rodent FDF03, YE01, or KTE03; 
 viii) exhibits at least two non-overlapping epitopes which are specific for a primate FDF03, YE01, or KTE03; 
 ix) exhibits a sequence identity at least about 90% over a length of at least about 20 amino acids to a primate FDF03, YE01, or KTE03; 
 x) is glycosylated; 
 xi) has a molecular weight of at least 7 kD with natural glycosylation; 
 xii) is a synthetic polypeptide; 
 xiii) is attached to a solid substrate; 
 xiv) is conjugated to another chemical moiety; 
 xv) is a 5-fold or less substitution from natural sequence; or 
 xvi) is a deletion or insertion variant from a natural sequence. 
   
     
     
         4 . A composition comprising:
 a) a sterile FDF03 protein or peptide of  claim 1 ;   b) said FDF03 protein or peptide 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; 
   c) a sterile YE01 protein or peptide of  claim 1 ;   d) said YE01 protein or peptide 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; 
   e) a sterile KTE03 protein or peptide of  claim 1 ; or   f) said KTE03 protein or peptide 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 protein of  claim 1 , comprising:
 a) mature protein sequence of Table 1, 2, or 3;   b) a detection or purification tag, including a FLAG, His6, or Ig sequence; or   c) sequence of another cell surface protein.   
     
     
         6 . A kit comprising a protein or polypeptide of  claim 1 , and:
 a) a compartment comprising said protein or polypeptide; and/or   b) instructions for use or disposal of reagents in said kit.   
     
     
         7 . A binding compound comprising an antigen binding portion from an antibody, which specifically binds to a natural FDF03, YE01, or KTE03 protein of  claim 1 , wherein:
 a) said protein is a rodent protein;   b) said binding compound is an Fv, Fab, or Fab2 fragment;   c) said binding compound is conjugated to another chemical moiety; or   d) said antibody:
 i) is raised against a peptide sequence of a mature polypeptide of Table 1, 2, or 3; 
 ii) is raised against a mature FDF03, YE01, or KTE03; 
 iii) is raised to a purified FDF03, YE01, or KTE03; 
 iv) is immuno selected; 
 v) is a polyclonal antibody; 
 vi) binds to a denatured FDF03, YE01, or KTE03; 
 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; and/or   b) instructions for use or disposal of reagents in said kit.   
     
     
         9 . The kit of  claim 8  capable of making a qualitative or quantitative analysis. 
     
     
         10 . 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. 
   
     
     
         11 . An isolated or recombinant nucleic acid encoding a protein or peptide or fusion protein of  claim 1 , wherein:
 a) said protein is from a Mammal, including a primate; or   b) said nucleic acid:
 i) encodes an antigenic peptide sequence of Table 1, 2, or 3; 
 ii) encodes a plurality of antigenic peptide sequences of Table 1, 2, or 3; 
 iii) exhibits at least about 80% identity 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 mammal, including a primate; 
 xi) comprises a natural full length coding sequence; 
 xii) is a hybridization probe for a gene encoding said protein; or 
 xiii) is a PCR primer, PCR product, or mutagenesis primer. 
   
     
     
         12 . A cell or tissue comprising a recombinant nucleic acid of  claim 11 . 
     
     
         13 . The cell of  claim 12 , 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.   
     
     
         14 . A kit comprising said nucleic acid of  claim 11 , and:
 a) a compartment comprising said nucleic acid;   b) a compartment further comprising a FDF03, YE01, or KTE03 protein or polypeptide; and/or   c) instructions for use or disposal of reagents in said kit.   
     
     
         15 . The kit of  claim 14  capable of making a qualitative or quantitative analysis. 
     
     
         16 . A nucleic acid which:
 a) hybridizes under wash conditions of 30° C. and less than 2M salt to the coding portion from SEQ ID NO:1 or 3;   b) hybridizes under wash conditions of 30° C. and less than 2 M salt to the coding portion from SEQ ID NO:5, 7, or 9;   c) hybridizes under wash conditions of 30° C. and less than 2M salt to the coding portion from SEQ ID NO:11, 13, 15, 17, 19, or 21;   d) exhibits at least about 85% identity over a stretch of at least about 30 nucleotides to a primate FDF03;   e) exhibits at least about 85% identity over a stretch of at least about 30 nucleotides to a primate YE01; or   f) exhibits at least about 85% identity over a stretch of at least about 30 nucleotides to a primate KTE03.   
     
     
         17 . The nucleic acid of  claim 16 , wherein:
 a) said wash conditions are at 45° C. and/or 500 mM salt; or   b) said identity is at least 90% and/or said stretch is at least 55 nucleotides.   
     
     
         18 . The nucleic acid of  claim 17 , wherein:
 a) said wash conditions are at 55° C. and/or 150 mM salt; or   b) said identity is at least 95% and/or said stretch is at least 75 nucleotides.   
     
     
         19 . A method of modulating physiology or development of a cell or tissue culture cell comprising contacting said cell with an agonist or antagonist of a FDF03, YE01, or KTE03. 
     
     
         20 . The method of  claim 19 , wherein the cell is a leukocyte, and the antagonist is to YE01 and is a monoclonal antibody which binds to DLAIR-1.