Mdl-1 ligand

Abstract

The invention provides methods for modulation interactions between MDL-1 and its binding partner, Gal9. Also provided are methods to screen for modulators of MDL-1/Gal9 interaction.

What is claimed is: 
     
         1 . A method of modulating an interaction between a lectin-like molecule expressed on myeloid cells, and a lectin which binds to a receptor expressed by a T cell, the method comprising:
 a) providing a compound that is capable of binding to lectin-like molecule at a binding site of the lectin; and   b) presenting the compound of step (i) to lectin-like molecule and the lectin and thereby modulating the interaction between the first and second lectin.   
     
     
         2 . The method of  claim 1 , wherein the lectin-like molecule is expressed by a macrophage cell. 
     
     
         3 . The method of  claim 1 , wherein the lectin-like molecule is MDL-1 and the lectin is Gal9. 
     
     
         4 . The method of  claim 1 , wherein the compound is selected from the group consisting of an antibody, a binding fragment of an antibody, and a soluble Ig fusion of the lectin-like molecule, wherein the compound modulates the interaction between the lectin-like molecule and the lectin. 
     
     
         5 . The method of  claim 4 , where in the compound binds MDL-1 and prevents the interaction of the lectin-like molecule with the lectin. 
     
     
         6 . A method of screening for a compound that modulates an interaction between a first lectin-like molecule expressed on myeloid cells, and a lectin which binds to a receptor expressed by a T cell, the method comprising:
 a) providing a compound that is capable of binding to the lectin-like molecule at a binding site of the lectin; and   b) presenting the compound of step (a) to the lectin-like molecule and the second lectin and thereby modulating the interaction between the first and second lectin.   
     
     
         7 . The method of  claim 6 , wherein the lectin-like is expressed by a macrophage cell. 
     
     
         8 . The method of  claim 6 , wherein lectin-like molecule is MLD-1 and the lectin is Gal9. 
     
     
         9 . The method of  claim 6 , wherein the compound is selected from the group consisting of an antibody, a binding fragment of an antibody, and a soluble Ig fusion of the lectin-like molecule. 
     
     
         10 . The method of  claim 9 , wherein the antibody or binding fragment of an antibody inhibits the interaction of the lectin-like molecule with the second lectin. 
     
     
         11 . The method of  claim 10 , wherein the antibody or binding fragment of the antibody inhibits phosphorylation of a signaling molecule associated with the second lectin. 
     
     
         12 . The method of  claim 11 , wherein the signaling molecule is selected from the group consisting of DAP12 and Syk and the phosphorylation is tyrosine phosphorylation. 
     
     
         13 . A method of depleting a population of T lymphocyte cells comprising contacting the population of T lymphocyte cells with an MDL-1 fusion protein that binds directly or indirectly to a molecule expressed on the T lymphocyte cells. 
     
     
         14 . The method of  claim 13 , wherein the MDL-1 fusion protein comprises an extracellular domain of MDL-1 and a heterologous protein. 
     
     
         15 . The method of  claim 14 , wherein the heterologous protein is an Fc portion of an immunoglobulin molecule. 
     
     
         16 . The method of  claim 14 , wherein the heterologous protein is human serum albumin. 
     
     
         17 . The method of  claim 13 , wherein the population of T lymphocyte cells express CD45, CD90, and CD117. 
     
     
         18 . The method of  claim 17 , wherein the population of T lymphocyte cells further express IL-23R. 
     
     
         19 . The method of  claim 18 , wherein the population of T lymphocyte cells mediate enthesopathy.