Human receptor proteins; related reagents and methods

Abstract

Nucleic acids encoding mammalian Toll-like receptors (TLRs) have been identified in human cells. Recombinantly produced TLRs are used in the preparation of antibodies that are capable of binding to the TLRs. The antibodies are advantageously used in the prevention and treatment of septic shock, inflammatory conditions, and viral infections.

1 . The isolated or recombinant polypeptide comprising the amino acid sequence of SEQ ID NO: 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 37, 39, 41, 43, or 45, or an antigenic fragment thereof. 
     
     
         2 . An isolated or recombinant nucleic acid encoding the polypeptide of  claim 1 . 
     
     
         3 . The nucleic acid of  claim 2 , further comprising an expression vector. 
     
     
         4 . A binding compound that specifically binds to the polypeptide or the antigenic fragment of  claim 1 . 
     
     
         5 . The binding compound of  claim 4 , wherein said binding compound comprises an antibody or antibody fragment. 
     
     
         6 . The binding compound of  claim 4 , wherein said binding compound further comprises a detectable label or a purification tag. 
     
     
         7 . The binding compound of  claim 4 , wherein said binding compound is attached to a solid support. 
     
     
         8 . A natural allelic variant of the polypeptide of  claim 1 . 
     
     
         9 . A binding compound that specifically binds to a ligand of SEQ ID NO: 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 37, 39, 41, 43, or 45. 
     
     
         10 . The binding compound of  claim 9 , wherein said binding compound is an antibody or antibody fragment. 
     
     
         11 . The binding compound of  claim 9 , wherein said binding compound is a soluble antigenic fragment of SEQ ID NO: 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 37, 39, 41, 43, or 45. 
     
     
         12 . The binding compound of  claim 9 , wherein said binding compound is detectably labeled. 
     
     
         13 . The binding compound of  claim 9 , wherein said binding compound further comprising an oligopeptide purification tag or a polypeptide purification tag. 
     
     
         14 . The binding compound of  claim 9 , wherein said binding compound is attached to a solid support. 
     
     
         15 . A method of treating a patient having sepsis or septic shock comprising administering to said patient a binding compound which binds specifically to a ligand of SEQ ID NO: 8. 
     
     
         16 . The method of  claim 15 , wherein said binding compound is an antibody, an antibody fragment, or a soluble antigenic fragment of SEQ ID NO: 8. 
     
     
         17 . A method of treating a patient having sepsis or septic shock comprising administering to said patient a binding compound which binds specifically to a ligand of SEQ ID NO: 26. 
     
     
         18 . The method of  claim 17 , wherein said binding compound is an antibody, an antibody fragment, or a soluble antigenic fragment of SEQ ID NO: 26. 
     
     
         19 . A method of treating a patient having an interferon-α treatable condition, comprising administering to the patient an antibody or antibody fragment which binds specifically to SEQ ID NO: 22 and activates SEQ ID NO: 22. 
     
     
         20 . The method of  claim 19 , wherein said interferon-α treatable condition is selected from hepatitis B, hepatitis C, hepatitis D, T-cell leukemia-lymphoma, multiple myeloma, chronic myeloid leukemia, and systemic lupus erythematosus. 
     
     
         21 . A method of treating a patient having an interferon-α treatable condition, comprising administering to the patient an antibody or antibody fragment which binds specifically to SEQ ID NO: 41 and activates SEQ ID NO: 41. 
     
     
         22 . The method of  claim 21 , wherein said interferon-α treatable condition is selected from hepatitis B, hepatitis C, hepatitis D, T-cell leukemia-lymphoma, multiple myeloma, chronic myeloid leukemia, and systemic lupus erythematosus.