Chemokine-binding protein and methods of use

Abstract

Described herein are chemokine-binding domains of THAP-family polypeptides and pharmaceutical compositions which include a polypeptide comprising a chemokine-binding domain of a THAP-family polypeptide. Also disclosed are methods of binding chemokines, inhibiting the activity of chemokines, detecting chemokines, and reducing the symptoms associated with a chemokine mediated or influenced condition by contacting the chemokine with an agent that includes a polypeptide comprising a chemokine binding domain of a THAP-family polypeptide.

1 . A method of inhibiting the activity of a chemokine, said method comprising contacting a chemokine with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO: 3, a polypeptide having at least 95% sequence identity to SEQ ID NO: 3, a chemokine-binding domain of SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein the activity of said chemokine is inhibited. 
     
     
         2 . The method of  claim 1 , wherein said polypeptide is selected from the group consisting of SEQ ID NO: 3 and a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         3 . The method of  claim 1 , wherein polypeptide is selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         4 . The method of  claim 1 , wherein said polypeptide is SEQ ID NO: 3. 
     
     
         5 . The method of  claim 1 , wherein said polypeptide has at least 95% sequence identity to SEQ ID NO: 3. 
     
     
         6 . The method of  claim 1 , wherein said polypeptide is a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         7 . The method of  claim 6 , wherein said chemokine-binding domain of SEQ ID NO: 3 comprises the amino acid sequence 143-213 of SEQ ID NO: 3. 
     
     
         8 . The method of  claim 1 , wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         9 . The method of  claim 1  further comprising administering a nucleic acid encoding said polypeptide to a subject. 
     
     
         10 . The method of  claim 1  further comprising administering said polypeptide to a subject. 
     
     
         11 . A method of inhibiting the activity of a chemokine, said method comprising contacting a chemokine selected from the group consisting of Secondary Lymphoid-tissue Chemokine (SLC), CCL19, CCL5, CXCL9 and CXCL10 with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO: 3, a polypeptide having at least 95% sequence identity to SEQ ID NO: 3, a chemokine-binding domain of SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein the activity of said chemokine is inhibited. 
     
     
         12 . The method of  claim 11 , wherein said chemokine is selected from the group consisting of SLC, CCL19 and CCL5. 
     
     
         13 . The method of  claim 11 , wherein said chemokine is selected from the group consisting of CXCL9 and CXCL10. 
     
     
         14 . The method of  claim 11 , wherein said chemokine is SLC. 
     
     
         15 . The method of  claim 11 , wherein said chemokine is CC19. 
     
     
         16 . The method of  claim 11 , wherein said chemokine is CCS. 
     
     
         17 . The method of  claim 11 , wherein said chemokine is CXCL9. 
     
     
         18 . The method of  claim 11 , wherein said chemokine is CXCL10. 
     
     
         19 . The method of  claim 11 , wherein said polypeptide selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein the activity of said chemokine is inhibited. 
     
     
         20 . The method of  claim 11 , wherein said polypeptide has at least 95% sequence identity to SEQ ID NO: 3. 
     
     
         21 . The method of  claim 11 , wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         22 . The method of  claim 21 , wherein said chemokine-binding domain of SEQ ID NO: 3 comprises the amino acid sequence 143-213 of SEQ ID NO: 3. 
     
     
         23 . The method of  claim 11  further comprising administering a nucleic acid encoding said polypeptide to a subject. 
     
     
         24 . The method of  claim 11  further comprising administering said polypeptide to a subject. 
     
     
         25 . A method of binding a chemokine, said method comprising contacting a chemokine with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO: 3, a polypeptide having at least 95% sequence identity to SEQ ID NO: 3, a chemokine-binding domain of SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein said chemokine is bound. 
     
     
         26 . The method of  claim 25 , wherein said polypeptide is selected from the group consisting of SEQ ID NO: 3 and a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         27 . The method of  claim 25 , wherein polypeptide is selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         28 . The method of  claim 25 , wherein said polypeptide is SEQ ID NO: 3. 
     
     
         29 . The method of  claim 25 , wherein said polypeptide has at least 95% sequence identity to SEQ ID NO: 3. 
     
     
         30 . The method of  claim 25 , wherein said polypeptide is a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         31 . The method of  claim 30 , wherein said chemokine-binding domain of SEQ ID NO: 3 comprises the amino acid sequence 143-213 of SEQ ID NO: 3. 
     
     
         32 . The method of  claim 25 , wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         33 . The method of  claim 25  further comprising administering a nucleic acid encoding said polypeptide to a subject. 
     
     
         34 . The method of  claim 25  further comprising administering said polypeptide to a subject. 
     
     
         35 . A method of binding a chemokine, said method comprising contacting a chemokine selected from the group consisting of Secondary Lymphoid-tissue Chemokine (SLC), CCL19, CCL5, CXCL9 and CXCL10 with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO: 3, a polypeptide having at least 95% sequence identity to SEQ ID NO: 3, a chemokine-binding domain of SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein said chemokine is bound. 
     
     
         36 . The method of  claim 35 , wherein said chemokine is selected from the group consisting of SLC, CCL19 and CCL5. 
     
     
         37 . The method of  claim 35 , wherein said chemokine is selected from the group consisting of CXCL9 and CXCL10. 
     
     
         38 . The method of  claim 35 , wherein said chemokine is SLC. 
     
     
         39 . The method of  claim 35 , wherein said chemokine is CC19. 
     
     
         40 . The method of  claim 35 , wherein said chemokine is CCS. 
     
     
         41 . The method of  claim 35 , wherein said chemokine is CXCL9. 
     
     
         42 . The method of  claim 35 , wherein said chemokine is CXCL10. 
     
     
         43 . The method of  claim 35 , wherein said polypeptide selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO: 3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3, wherein the activity of said chemokine is inhibited. 
     
     
         44 . The method of  claim 35 , wherein said polypeptide has at least 95% sequence identity to SEQ ID NO: 3. 
     
     
         45 . The method of  claim 35 , wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO: 3. 
     
     
         46 . The method of  claim 45 , wherein said chemokine-binding domain of SEQ ID NO: 3 comprises the amino acid sequence 143-213 of SEQ ID NO: 3. 
     
     
         47 . The method of  claim 35  further comprising administering a nucleic acid encoding said polypeptide to a subject. 
     
     
         48 . The method of  claim 35  further comprising administering said polypeptide to a subject.