Multivalent MHC class II - peptide chimeras
AssigneeMount Sinai School of Medicine of the City of New York
InventorsTeodor Doru Brumeanu, Sofia Casares, Constantin A. Bona
Life of this patent
Estimating the term…
Abstract
The present invention provides a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker. Methods of making and using the multimeric complexes are also provided.
Claims17
A multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker.
A multimeric complex of at least two chimeric molecules wherein each chimeric molecule comprises:
- an immunoglobulin constant region element having two chains covalently joined by a disulfide linkage wherein the chains comprise the CH3, CH2 and hinge domains;
- two MHC class II elements comprising the extracellular domains of the α and β chains, wherein each of the MHC elements is covalently linked via the α or β chain to a chain of the immunoglobulin constant region element;
- and a peptide covalently linked or fused to the MHC element;
- and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyethylene glycol linker.
A method of making a multimeric complex comprising at least two chimeric molecules wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements, wherein each MHC element is associated with a peptide, said method comprising:
- contacting said chimeric molecules with one or more neuraminidases under conditions to desialylate carbohydrate residues of the immunoglobulin constant region element to provide desialylated chimeric molecules;
- contacting the desialylated chimeric molecules with galactose oxidase and diamino-polyalkylene glycol under conditions to covalently link two or more chimeric molecules, and subjecting the covalently linked molecules to reducing conditions to stabilize Schiff bases.
A composition comprising a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker.
A method of modulating T cell function comprising administering to a subject a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker.
A method of diagnosing an autoimmune disorder in a subject comprising isolating T cells from a subject and determining the number of T cells that react with a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker, and wherein the peptide of interest is associated with the autoimmune disorder
Dependencies are inferred from the claim text.