Methods and compositions for using mhc class ii invariant chain polypeptides as a receptor for macrophage migration inhibitory factor
AssigneeBaxalta Incorporated
InventorsRichard J. Bucala, Lin Leng, Christine N. Metz
Life of this patent
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Abstract
Methods and compositions for using the MEW class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.
Claims23
A method for screening compounds for an agonist or antagonist of MIF comprising:
- contacting an WIC class II invariant chain (Ii) polypeptide with MIF in the presence and absence of a candidate compound, and
- comparing the interaction of the MIF and said Ii polypeptide in the presence of said candidate compound with their interaction in the absence of said candidate compound, whereby
- a candidate compound that enhances the interaction of said MIF with said Ii polypeptide is identified as an agonist of MIF, and
- a candidate compound that inhibits the interaction of said MIF with said Ii polypeptide is identified as an antagonist of MIF;
- wherein said Ii polypeptide comprises the complete Ii amino acid sequence of FIG. 5 (SEQ ID. NO:2) or an MIF-binding fragment thereof.
A method of inhibiting an effect of MIF on a cell comprising on its surface an MEW class II invariant chain (Ii) polypeptide which binds MIF and thereby mediates said effect of MIF, said method comprising:
- contacting said cell with an antagonist of MIF wherein said antagonist inhibits binding of MIF to said Ii polypeptide.
-12. (canceled)
A method of inhibiting an activity of MIF, said method comprising:
- contacting MIF with an antagonist of MIF, wherein said antagonist of MIF comprises a MEW class II invariant chain (Ii) polypeptide or a fragment thereof which binds to MIF.
-20. (canceled)
A method of purifying MIF comprising:
- contacting a sample comprising MIF with an MHC class II invariant chain (Ii) polypeptide or a fragment thereof which binds to MIF under conditions that promote the specific binding of MIF to the Ii polypeptide or fragment thereof, and
- separating the MIF:Ii polypeptide complex or MIF:Ii polypeptide fragment complex thereby formed from materials which do not bind to the Ii polypeptide or fragment thereof.
(canceled)
A method of assaying for the presence of MIF comprising:
- contacting a sample with an MHC class H invariant chain (Ii) polypeptide or a fragment thereof which binds to MIF under conditions that promote the specific binding of MIF to said Ii polypeptide or a fragment thereof, and
- detecting any MIF:Ii polypeptide complex or MIF:Ii polypeptide fragment complex thereby formed.
A method for reducing an effect of MIF on a cell comprising on its surface an MEW class II invariant chain (Ii) polypeptide which binds MIF and thereby mediates said effect of MIF, said method comprising:
- providing to said cell an antisense nucleic acid molecule in an amount effective to reduce the amount of said Ii polypeptide produced by said cell,
- wherein said antisense nucleic acid molecule specifically binds to a portion of mRNA expressed from a gene encoding said MEW class II invariant chain (Ii) polypeptide and thereby decreases translation of said mRNA in said cell.
-28. (canceled)
Dependencies are inferred from the claim text.