Ligand (ACT-4-L) to a Receptor on the Surface of Activated CD4+ T-Cells

Abstract

The invention provides ligands and fragments thereof to a receptor on the surface of activated CD4 + T-cells. An exemplary ligand is designated ACT-4-L-h-1. Preferred fragments include purified extracellular domains of ligands. The invention also provides humanized and human antibodies to the ligand. The invention further provides methods of using the ligand and the antibodies in treatment of diseases and conditions of the immune system. The invention also provides methods of monitoring activated CD4 + T-cells using the ligands or fragments thereof.

1 . A purified ACT-4-L ligand polypeptide having a segment between 5 and 160 contiguous amino acids from an amino acid sequence shown in  FIG. 10 . 
     
     
         2 . The polypeptide of  claim 1  that exhibits at least eighty percent sequence identity to the amino acid sequence of  FIG. 10 . 
     
     
         3 . The polypeptide of  claim 2  having an antigenic determinant common to a protein with the amino acid sequence shown in  FIG. 10 . 
     
     
         4 . The polypeptide of  claim 3  comprising an intracellular domain, a transmembrane domain, or an extracellular domain. 
     
     
         5 . The polypeptide of  claim 1  that comprises an extracellular domain of an ACT-4-L ligand. 
     
     
         6 . The polypeptide of  claim 1  that is glycosylated. 
     
     
         7 . The polypeptide of  claim 6  further comprising a linked second polypeptide. 
     
     
         8 . The polypeptide of  claim 7 , wherein the second polypeptide is an immunoglobulin constant domain. 
     
     
         9 . A purified extracellular domain of an ACT-4-L ligand comprising at least five contiguous amino acids from the full-length ACT-4-L-h-1 extracellular domain. 
     
     
         10 . The extracellular domain of  claim 9  that is full-length. 
     
     
         11 . The extracellular domain of  claim 9  that is in soluble form. 
     
     
         12 . The extracellular domain of  claim 11  that specifically binds to the ACT-4-L-h-1 ligand. 
     
     
         13 . The extracellular domain of  claim 11  that specifically binds to the ACT-4-h-1 receptor. 
     
     
         14 . The extracellular domain of  claim 13  consisting essentially of a domain that specifically binds to the ACT-4-h-1 receptor. 
     
     
         15 . The extracellular domain of  claim 9  that is labelled. 
     
     
         16 . The extracellular domain of  claim 9  that inhibits in vitro activation of CD4+ T cells expressing the ACT-4-h-1 receptor on their surface. 
     
     
         17 . The extracellular domain of  claim 9  that stimulates in vitro activation of CD4+ T cells expressing the ACT-4-h-1 receptor on their surface. 
     
     
         18 . The extracellular domain of  claim 9  that competes with an antibody designated L106 for specific binding to the ACT-4-h-1 receptor. 
     
     
         19 . The extracellular domain of  claim 9  that competes with the ACT-4-L-h-1 ligand for binding to an antibody. 
     
     
         20 . The extracellular domain of  claim 9  further comprising a linked second polypeptide. 
     
     
         21 - 50 . (canceled)