Immunogenic peptides and their use in immune disorders

Abstract

The present invention provides novel peptides and homologues thereof. The peptides of the invention comprise (i) a T-cell epitope of an antigen (self or non-self) with a potential to trigger an immune reaction presented by a class II major histocompatibility complex (MHC) determinant and recognised by CD4+ T cell more specifically of an allergen or auto-antigen, coupled, optionally through the use of a linker to (ii) an amino acid sequence having a reducing activity, such as a thioreductase sequence. The peptides of the invention have been shown to be useful a medicine, more in particular for the prevention or treatment of immune disorders, more specifically of allergic disorders or autoimmune diseases. The present invention thus provides for the use of said peptides for the manufacture of a medicament for the prevention or treatment of an immune disorder and further provides for methods of treatment or preventing immune disorders by using said peptides. The present invention also provides for compositions comprising said peptides.

1 - 36 . (canceled) 
     
     
         37 . A population of T regulatory cells obtained by a method comprising the step of:
 contacting peripheral blood cells with an immunogenic peptide comprising an artificial sequence comprising: (i) a T cell epitope of an antigenic protein; and (ii) a redox motif C-X(2)-[CST] or [CST]-X(2)-C, said motif being either adjacent to said epitope, or separated from said epitope by a linker of at most 7 amino acids.   
     
     
         38 . The population of T regulatory cells according to  claim 37 , wherein the method comprises the steps of:
 providing peripheral blood cells,   contacting said cells with an immunogenic peptide comprising an artificial sequence comprising: (i) a T cell epitope of an antigenic protein; and (ii) a redox motif C-X(2)-[CST] or [CST]-X(2)-C, said motif being either adjacent to said epitope, or separated from said epitope by a linker of at most 7 amino acids, and   expanding said cells in the presence of IL-2.   
     
     
         39 . The population of T regulatory cells according to  claim 38 , wherein the method is an in vitro method. 
     
     
         40 . The population of T regulatory cells according to  claim 37 , wherein the method comprises the steps of:
 providing an immunogenic peptide comprising an artificial sequence comprising: (i) a T cell epitope of an antigenic protein; and (ii) a redox motif C-X(2)-[CST] or [CST]-X(2)-C, said motif being either adjacent to said epitope, or separated from said epitope by a linker of at most 7 amino acids;   administering said peptide to a subject, and   obtaining said population of antigen-specific regulatory T cells from said subject.   
     
     
         41 . The population of T regulatory cells according to  claim 37 , wherein said immunogenic peptide is a peptide with a length of at most 75 amino acids. 
     
     
         42 . The population of T regulatory cells according to  claim 41 , wherein said immunogenic peptide is a peptide having a length of from 12 to 75 amino acids. 
     
     
         43 . The population of T regulatory cells according to  claim 37 , wherein said T cell epitope is an MHC class II T cell epitope of an allergen or auto-antigen. 
     
     
         44 . The population of T regulatory cells according to  claim 43 , wherein the sequence of said allergen or auto-antigen does not comprise a C-X(2)-[CST] or [CST]-X(2)-C redox motif within a sequence of 11 amino acids N or C terminal of said epitope. 
     
     
         45 . The population of T regulatory cells according to  claim 43 , wherein said auto-antigen is selected from the group consisting of thyroglobulin, thyroid peroxidase, TSH receptor, insulin, proinsulin, glutamic acid decarboxylase (GAD), tyrosine phosphatase IA-2, heat-shock protein HSP65, islet-specific glucose 6-phosphatase catalytic subunit related protein (IGRP), 21-OH hydroxylase, 17-alpha hydroxylase, histidine decarboxylase, tryptophan hydroxylase, tyrosine hydroxylase, H+/K+ ATPase intrinsic factor, myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), proteolipid protein (PLP), acetyl-choline receptor, retinol-binding protein (RBP), type II collagen, type IX collagen, tissue transglutaminase, pANCA histone H1 protein and heat-shock protein HSP60. 
     
     
         46 . The population of T regulatory cells according to  claim 37 , wherein said redox motif is separated from said T cell epitope by a linker of at most 4 amino acids. 
     
     
         47 . The population of T regulatory cells according to  claim 37 , wherein said redox motif is positioned N-terminally of said T cell epitope sequence. 
     
     
         48 . The population of T regulatory cells according to  claim 37 , wherein said cells are cytolytic T regulatory cells. 
     
     
         49 . The population of T regulatory cells according to  claim 37 , wherein said cells produce granzyme B. 
     
     
         50 . The population of T regulatory cells according to  claim 37 , wherein said redox motif is C-X(2)-C. 
     
     
         51 . A pharmaceutical composition comprising the T regulatory cells of  claim 37  and a pharmaceutically acceptable carrier. 
     
     
         52 . A method of treating an allergic condition or an autoimmune disorder comprising administering the population of T regulatory cells according to  claim 37  to a subject in need thereof. 
     
     
         53 . The method of treating an autoimmune disorder according to  claim 52 , wherein the autoimmune disease is selected from the group of diseases consisting of: thyroid diseases, type 1 diabetes, adrenalitis, polyendocrine syndromes, gastritis & pernicious anemia, multiple sclerosis, myasthenia gravis, ocular diseases, inner ear diseases, celiac disease, inflammatory bowel diseases, and atherosclerosis. 
     
     
         54 . A method of treating an allergic condition or an autoimmune disorder comprising administering the pharmaceutical composition according to  claim 51  to a subject in need thereof. 
     
     
         55 . The method of treating an autoimmune disorder according to  claim 54 , wherein the autoimmune disease is selected from the group of diseases consisting of: thyroid diseases, type 1 diabetes, adrenalitis, polyendocrine syndromes, gastritis & pernicious anemia, multiple sclerosis, myasthenia gravis, ocular diseases, inner ear diseases, celiac disease, inflammatory bowel diseases, and atherosclerosis.