Pegylated CD154 peptides and methods of inhibiting CD40 interacations with CD154
View Patent ↗The present invention provides methods and materials for treating and preventing autoimmune diseases. In particular, the present invention relates to the discovery that small peptides are capable of interacting with CD40, thereby interfering with the ability of CD40 to interact with CD 154, which is important in inflammation. The present invention also relate to the use of such peptides in reducing the inflammatory response, and in particular, the autoimmune inflammatory response. The present invention also relates to the use of such short peptides to prevent or reverse autoimmune disease, and particular, diabetes, in individuals suffering from such disease. It also relates to methods and materials for detecting T-cells that express CD40 (Th40 cells). Also provided are kits for reducing inflammation, treating autoimmune diseases, or detecting Th40 cells.
1. A pegylated peptide consisting of SEQ ID NO:8 that inhibits the binding of CD40 with CD154/gp39/CD40-ligand.
2. The peptide of claim 1 , wherein said peptide binds to CD40.
3. The peptide of claim 1 , wherein said peptide binds to a CD40 protein with a Kd of greater than 10 6 .
4. The peptide of claim 1 , wherein said peptide inhibits the binding of CD40 and CD154.
5. The peptide of claim 1 , wherein said peptide binds CD40 at the site where CD40 interacts with CD154.
6. The peptide of claim 1 , wherein said peptide inhibits the expansion of Th40 cells.
7. The peptide of claim 1 , wherein said peptide alters the cytokine expression profile of a cell population treated with said peptide.
8. A method to inhibit the interaction between a CD40 protein and a CD154 protein comprising contacting said CD40 protein with a pegylated peptide of claim 1 that binds said CD40 protein at the CD154-binding site, thereby inhibiting the interaction of said CD40 and CD154 proteins.
9. A method of reducing the number of Th40 cells in a patient comprising administering to the patient a pegylated peptide of claim 1 that inhibits the interaction of CD40 and CD154.