Compositions and methods for the prevention and treatment of autoimmune conditions

Abstract

The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and/or ameliorate autoimmune diseases.

1 . A method of treating an autoimmune disorder in a subject in need thereof comprising administering to the subject a peptide-MHC complex operatively coupled to a non-liposomal nanoparticle in an amount sufficient to expand low avidity anti-pathogenic autoreactive T cells; and wherein the MHC is a non-classical MHC; and wherein the nanoparticle has a diameter of less than 1 μm. 
     
     
         2 . The method of  claim 1 , wherein the antigen is a peptide, a carbohydrate, a lipid, or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein the autoimmune disorder is diabetes melitus, prediabetes, multiple sclerosis, premature ovarian failure, scleroderm, Sjogren's disease, lupus, vilelego, alopecia (baldness), polyglandular failure, Grave's disease, hypothyroidism, polymyosititis, pemphigus, Chron's disease, colititis, autoimmune hepatitis, hypopituitarism, myocardititis, Addison's disease, autoimmune skin diseases, uveititis, pernicious anemia, hypoparathyroidism, or rheumatoid arthritis. 
     
     
         4 . The method of  claim 3 , wherein the antigen is derived from an autoantigen involved in the autoimmune response or a mimic thereof. 
     
     
         5 . The method of  claim 1 , wherein the autoantigen is an epitope from an antigen expressed by pancreatic beta cells. 
     
     
         6 . The method of  claim 5 , wherein the autoantigen is IGRP, Insulin, GAD or IA-2 protein. 
     
     
         7 . The method of  claim 5 , wherein the autoantigen is an epitope derived from a second endocrine or neurocrine component. 
     
     
         8 . The method of  claim 7  wherein the second endocrine or neuroendocrine component is peri-islet Schwann cells. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 9 , wherein the MHC class I component comprises all or part of a HLA-E, HLA-F, HLA-G, HFE, MICA, MICB, Qa-1 or CD-1 molecule. 
     
     
         11 . The method of  claim 1 , wherein, the MHC class I component comprises all or part of a HLA-A molecule. 
     
     
         12 . The method of  claim 1 , wherein the MHC class I component comprises all or part of a HLA-A*0201 MHC class I molecule. 
     
     
         13 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the nanoparticle comprises a metal. 
     
     
         18 . The method of  claim 17 , wherein the metal is iron. 
     
     
         19 . The method of  claim 1 , wherein the antigen is covalently coupled to MHC component. 
     
     
         20 . The method of  claim 19 , wherein the complex is coupled to the substrate via a linker. 
     
     
         21 . The method of  claim 20 , wherein the linker is a peptide linker. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the administration of the antigen-MHC complex is prior to the onset of clinical symptoms of autoimmune disease. 
     
     
         25 . The method of  claim 1 , wherein the administration of the antigen-MHC complex is after to the onset of clinical symptoms of autoimmune disease. 
     
     
         26 . The method of  claim 1 , further comprising assessing the subject's blood sugar levels before and after treatment. 
     
     
         27 . The method of  claim 1 , further comprising assessing a subject's autoimmune status. 
     
     
         28 . The method of  claim 1 , wherein the T cell is a CD4+ or CD8+ T cell. 
     
     
         29 .- 46 . (canceled) 
     
     
         47 . The method of  claim 1 , wherein the method treats type I diabetes. 
     
     
         48 . The method of  claim 1 , wherein the method treats prediabetes.