Carbohydrate Ligands Specific For MHC Molecules

Abstract

The present invention provides a substantially purified carbohydrate ligand that specifically binds to a leczyme. The invention also provides methods to identify a carbohydrate ligand that specifically binds to a leczyme or a leczyme that specifically binds to a carbohydrate ligand. The invention further provides methods to identify a peptide that binds to the carbohydrate ligand binding site of a leczyme. The present invention provides methods to isolate a carbohydrate ligand or a leczyme and to identify a carbohydrate ligand or a leczyme that modifies the function of a cell and to obtain such functionally modified cells. The invention further provides methods to modify a cell to express a carbohydrate ligand by introducing an expression vector encoding a leczyme into the cell. The invention also provides methods to modulate the immune response to an antigen by administering the antigen and a carbohydrate ligand. In addition, the invention further provides methods to treat a disease state involving a leczyme by administering a carbohydrate ligand that binds the leczyme or by administering a leczyme that has a similar binding specificity to the leczyme involved in the disease state. The invention further provides methods to diagnose a genetic basis for hemochromatosis by detecting a mutation in a class I MHC molecule that reduces it's ability to associate with β 2 microglobulin.

1 - 78 . (canceled) 
     
     
         79 . A method of identifying a ligand of a leczyme, the ligand having a carbohydrate portion, comprising the steps of:
 identifying a polypeptide as a leczyme, wherein the step of identifying is based on actual or suspected (a) catalytic activity that allows the leczyme to chemically modify the carbohydrate portion and (b) affinity to the carbohydrate portion to allow the leczyme to bind to the ligand;   contacting a compound suspected to be the ligand with the leczyme; and   detecting binding of compound to the leczyme, wherein binding is indicative of the compound as being the ligand of the leczyme.   
     
     
         80 . The method of  claim 79 , wherein the leczyme is an MHC-derived gene product. 
     
     
         81 . The method of  claim 80 , wherein the MHC-derived gene product is a class I molecule. 
     
     
         82 . The method of  claim 80 , wherein the MHC-derived gene product is a class II molecule. 
     
     
         83 . The method of  claim 80 , wherein the MHC-derived gene product is a nonclassical class I molecule. 
     
     
         84 . The method of  claim 79 , wherein the leczyme is a gene product of a gene in an immunoglobulin gene superfamily. 
     
     
         85 . The method of  claim 79 , wherein the ligand further comprises a polypeptide or lipid moiety bound to the carbohydrate portion. 
     
     
         86 . The method of  claim 79 , wherein at least one of the ligand or the leczyme includes a detectable label. 
     
     
         87 . The method of  claim 79 , wherein the ligand or the leczyme is associated with a cell. 
     
     
         88 . A composition, comprising a ligand identified by the method of  claim 79 , wherein the ligand has composition and structure effective to bind to the leczyme. 
     
     
         89 . The composition of  claim 88 , wherein the ligand further comprises a polypeptide or lipid moiety. 
     
     
         90 . A method for modulating an immune response in an individual to an antigen, comprising administering the ligand of  claim 88  and the antigen. 
     
     
         91 . The method of  claim 90 , wherein the step of administering results in an increase in the immune response to the antigen. 
     
     
         92 . The method of  claim 90 , wherein the step of administering results in a decrease in the immune response to the antigen. 
     
     
         93 . The method of  claim 90 , wherein the step of administering further comprises administering an immune suppressing agent. 
     
     
         94 . The method of  claim 90 , wherein the antigen and the ligand are covalently bound to each other. 
     
     
         95 . The method of  claim 90 , further comprising a step of administering an adjuvant with the antigen and the ligand. 
     
     
         96 . A method of manipulating a cell to thereby enable the cell to produce a compound having a carbohydrate ligand, comprising:
 introducing into the cell an expression vector encoding a leczyme polypeptide wherein the vector is configured to allow expression of the leczyme polypeptide; and   ascertaining that the cell produces the compound having the carbohydrate ligand as a function of the expression of the expression vector.   
     
     
         97 . The method of  claim 96 , wherein the leczyme is an MHC-derived gene product. 
     
     
         98 . The method of  claim 90 , wherein the leczyme is a non-MHC derived gene product.