Dendritic cell receptor

Abstract

The invention provides isolated human DEC-205, its extracellular domain and functionally equivalent fragments thereof. Also provided are polynucleotides encoding same and vectors which include such polynucleotides. Further provided are methods of recombinantly producing human DEC-205, an extracellular domain thereof or a functionally equivalent fragment, and ligands that bind to human DEC-205 or a fragment thereof. Also provided are constructs for use in prophylaxis or therapy comprising such a ligand, human DEC-205 or an extracellular domain thereof coupled to a toxin or to an antigen capable of inducing a protective immune response in a patient.

1 . Isolated human DEC-205 which has an approximate molecular weight of 198-205 kDa and which includes the following amino acid sequences: 
 (i) TVDCNDNQPGAICYYSGNETEKEVKPVDSVKCPSPVLNTPWIPF QNCCYNFIITKNRHMATTQDEVQSTCEKLHPKSHILSIRDEKE NNFVLEQLLYFNYMASWVMLGITYRNNSL; and    (ii) SQHRLFHLHSQKCLGLDITKSVNELRMFSCDSSAML;    or a functionally equivalent fragment thereof.    
     
     
         2 . Isolated human DEC-205 which comprises the amino acid sequence of FIG. 11, or a functionally equivalent fragment thereof.  
     
     
         3 . Isolated human DEC-205 in mature form which comprises amino acids 27 to 1722 of the amino acid sequence of FIG. 11.  
     
     
         4 . The extracellular domain of human DEC-205 or a functionally equivalent fragment thereof as claimed in  claim 1 .  
     
     
         5 . The extracellular domain of human DEC-205 having an amino acid sequence which includes amino acids 27 to 1661 of FIG. 11 or a functionally equivalent fragment thereof.  
     
     
         6 . An extracellular domain fragment as claimed in  claim 5  which includes amino acids 1208 to 1323 of amino acid sequence of FIG. 11.  
     
     
         7 . A polynucleotide encoding human DEC-205, its extracellular domain or a fragment thereof as defined in any one of  claims 1  to  6 .  
     
     
         8 . A polynucleotide as claimed in  claim 7  which includes the following nucleotide sequences:  
       
         
           
                 
                 
               
                     
                 
                   (iii) 
                     A ACA GTT GAT TGC AAT GAC AAT CAA CCA GGT 
                 
                     
                 
                     
                   GCT ATT TGC TAC TAT TCA GGA AAT GAG ACT GAA 
                 
                     
                 
                     
                   AAA GAG GTC AAA CCA GTT GAC AGT GTT AAA TGT 
                 
                     
                 
                     
                   CCA TCT CCT GTT CTA AAT ACT CCG TGG ATA CCA 
                 
                     
                 
                     
                   TTT CAG AAC TGT TGC TAC AAT TTC ATA ATA ACA 
                 
                     
                 
                     
                   AAG AAT AGG CAT ATG GCA ACA ACA CAG GAT GAA 
                 
                     
                 
                     
                   GTT CAT ACT AAA TGC CAG AAA CTG AAT CCA AAA 
                 
                     
                 
                     
                   TCA CAT ATT CTG AGT ATT CGA GAT GAA AAG GAG 
                 
                     
                 
                     
                   AAT AAC TTT GTT CTT GAG CAA CTG CTG TAC TTC 
                 
                     
                 
                     
                   AAT TAT ATG GCT TCA TGG GTC ATG TTA GGA ATA 
                 
                     
                 
                     
                   ACT TAT AGA AAT AAX TCT CTT; and 
                 
                     
                 
                   (iv) 
                   ATT AAT ATG CTG TGG AAG TGG GTG TCC CAG CAT 
                 
                     
                 
                     
                   CGG CTC TTT CAT TTG CAC TCC CAA AAG TGC CTT 
                 
                     
                 
                     
                   GGC CTC GAT ATT ACC AAA TCG GTA AAT GAG CTG 
                 
                     
                 
                     
                   AGA ATG TTC AGC TGT GAC TCC AGT GCC ATG CTG 
                 
                     
                 
                     
                   TGG TGG AAA TGC GAG CAC CA 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein X is T or G.  
     
     
         9 . A polynucleotide as claimed in  claim 7  which comprises all of the nucleotide sequence of FIG. 10.  
     
     
         10 . A polynucleotide as claimed in  claim 7  which comprises nucleotides 64 to 5166 of the nucleotide sequence of FIG. 10.  
     
     
         11 . A polynucleotide as claimed in any one of  claims 7  to  10  which is DNA.  
     
     
         12 . A vector which includes a polynucleotide as claimed in  claim 12 .  
     
     
         13 . A method of producing human DEC-205, an extracellular domain thereof or a functionally equivalent fragment comprising the steps of: 
 (a) culturing a host cell which has been transformed or transfected with a vector as defined above to express the encoded human DEC-205, extracellular domain or fragment; and    (b) recovering the expressed human DEC-205, extracellular domain or fragment    
     
     
         14 . A ligand that binds to human DEC-205 or a fragment thereof as claimed in any one of  claims 1  to  3 .  
     
     
         15 . A ligand that binds to an extracellular domain of human DEC-205 or fragment thereof as claimed in any one of  claims 4  to  6 .  
     
     
         16 . A ligand as claimed in  claim 14  or  claim 15  which is an antibody, or antibody binding fragment.  
     
     
         17 . A construct for use in prophylaxis or therapy comprising a ligand as claimed in any one of  claims 14  to  16  coupled to an antigen capable of inducing protective immune response in a patient.  
     
     
         18 . A construct for use in prophylaxis or therapy comprising a ligand as claimed in any one of  claims 14  to  16  coupled to a toxin.  
     
     
         19 . A construct for use in prophylaxis or therapy comprising human DEC-205 or an extracellular domain thereof as claimed in any one of  claims 1  to  6  coupled to an antigen capable of inducing a protective immune response in a patient.  
     
     
         20 . A construct for use in prophylaxis or therapy comprising human DEC-205 or an extracellular domain thereof as claimed in any one of  claims 1  to  6  coupled to a toxin.  
     
     
         21 . A method of prophylaxis or therapy which comprises administering to a patient in need of the same human DEC-205 as claimed in any one of  claims 1  to  3 , an extracellular domain as claimed in any one of  claims 4  to  6 , a ligand as claimed in any one of  claims 14  to  16 , or a construct as claimed in any one of  claims 17  to  20 .  
     
     
         22 . A process for isolating activated dendritic cells expressing human DEC-205 on the surface thereof comprising the step of contacting a sample containing said cells with a ligand as claimed in  claim 16 , and isolating those cells to which the ligand has bound.