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 .- 46 . (canceled) 
     
     
         47 . A nanoparticle complex comprising a nanoparticle core and an autoantigen peptide-MHC complex covalently coupled to the nanoparticle core,
 wherein the nanoparticle core has a diameter of less than 1 μm; and   wherein the ratio of autoantigen peptide-MHC complexes coupled to the nanoparticle core is from 10:1 to 1000:1; and   wherein the nanoparticle core comprises a metal, a metal oxide, a metal sulfide, a metal selenide, a magnetic material, gold, iron, or iron oxide.   
     
     
         48 . The nanoparticle complex of  claim 47 , wherein the surface of the nanoparticle core further comprises a layer. 
     
     
         49 . The nanoparticle complex of  claim 47 , wherein the MHC molecule of the autoantigen peptide-MHC complexes comprises an MHC class I or MHC class II molecule. 
     
     
         50 . The nanoparticle complex of  claim 49 , wherein the MHC class I molecule comprises all or part of a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G or CD-1 molecule. 
     
     
         51 . The nanoparticle complex of  claim 49 , wherein the MHC class II molecule comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP molecule. 
     
     
         52 . The nanoparticle complex of  claim 51 , wherein the MHC class II molecule comprises all or part of a HLA-DR molecule. 
     
     
         53 . The nanoparticle complex of  claim 47 , wherein the ratio of number of autoantigen peptide-MHC complexes to the nanoparticle core is from 10:1 to 100:1. 
     
     
         54 . The nanoparticle complex of  claim 47 , wherein the complexes are covalently attached to the core via a linker. 
     
     
         55 . The nanoparticle complex of  claim 54 , wherein the linker is ethylene glycol. 
     
     
         56 . The nanoparticle complex of  claim 48 , wherein the complexes are covalently attached to the layer via a linker. 
     
     
         57 . The nanoparticle complex of  claim 56 , wherein the linker is ethylene glycol. 
     
     
         58 . The nanoparticle complex of  claim 47 , wherein the autoantigen peptide is derived from GAD65 114-123 , VMNILLQYVV (SEQ ID NO:14); GAD65 536-545 , RMMEYGTTMV (SEQ ID NO:15); GFAP 143-151 , NLAQTDLATV (SEQ ID NO:16); GFAP 214-222 , QLARQQVHV (SEQ ID NO:17); IA-2 172-180 , SLSPLQAEL (SEQ ID NO:18); IA-2 482-490 , SLAAGVKLL (SEQ ID NO:19); IA-2 805-813 , VIVMLTPLV (SEQ ID NO:20); ppIAPP 5-13 , KLQVFLIVL (SEQ ID NO:21); ppIAPP 9-17 , FLIVLSVAL (SEQ ID NO:22); IGRP 152-160 , FLWSVFMLI (SEQ ID NO:23); IGRP 211-219 , NLFLFLFAV (SEQ ID NO:24); IGRP 215-223 , FLFAVGFYL (SEQ ID NO:25); IGRP 222-230 , YLLLRVLNI (SEQ ID NO:26); IGRP 228-236 , LNIDLLWSV (SEQ ID NO:2); IGRP 265-273 , VLFGLGFAI (SEQ ID NO:3); IGRP 293-301l , RLLCALTSL (SEQ ID NO:27); Pro-insulin L2-10 , ALWMRLLPL (SEQ ID NO:28); Pro-insulin L3-11 , LWMRLLPLL (SEQ ID NO:29); Pro-insulin L6-14 , RLLPLLALL (SEQ ID NO:30); Pro-insulin B5-14 , HLCGSHLVEA (SEQ ID NO:31); Pro-insulin B10-18 , HLVEALYLV (SEQ ID NO:1); Pro-insulin B14-22 , ALYLVCGER (SEQ ID NO:32); Pro-insulin B15-24 , LYLVCGERGF (SEQ ID NO:33); Pro-insulin B17-25 , LVCGERGFF (SEQ ID NO:34); Pro-insulin B18-27 , VCGERGFFYT (SEQ ID NO:35); Pro-insulin B20-27 , GERGFFYT (SEQ ID NO:36); Proinsulin B21-29 , ERGFFYTPK (SEQ ID NO:37); Pro-insulin B25-C1 , FYTPKTRRE (SEQ ID NO:38); Pro-insulin B27-C5 , TPKTRREAEDL (SEQ ID NO:39); Pro-insulin C20-28 , SLQPLALEG (SEQ ID NO:40); Pro-insulin C25-33 , ALEGSLQKR (SEQ ID NO:41); Pro-insulin C29-A5 , SLQKRGIVEQ (SEQ ID NO:42); Pro-insulin A1-10 , GIVEQCCTSI (SEQ ID NO:43); Pro-insulin- A2-10 , IVEQCCTSI (SEQ ID NO:44); Pro-insulin A12-20 , SLYQLENYC (SEQ ID NO:45) or combinations thereof. 
     
     
         59 . The nanoparticle complex of  claim 47 , wherein the nanoparticle core comprises gold, iron, or iron oxide.