Immunogenic peptides for use in the prevention and/or treatment of infectious diseases, autoimmune diseases, immune responses to allofactors, allergic diseases, tumors, graft rejection and immune responses against viral vectors used for gene therapy or gene vaccination

Abstract

The invention describes new peptides containing epitopes recognized by CD4+ natural killer T (NKT) cells for increasing activity for use in infectious diseases, autoimmune diseases, immune reaction to administration of allofactors, allergic diseases, therapy of tumors, prevention of graft rejection and prevention of immunization against viral proteins used in gene therapy or gene vaccination.

1 - 16 . (canceled) 
     
     
         17 . An in vitro method for detecting or depleting CD4+ T lymphocytes, comprising contacting the CD4+ T lymphocytes with an isolated immunogenic peptide comprising:
 (1) a natural killer T (NKT) cell epitope having a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] (SEQ ID NO: 23) motif of an antigenic protein;   (2) a thioreductase [C, S or T]-XX-C (SEQ ID NO: 19) or C-XX-[C, S or T] (SEQ ID NO: 18) motif, which is either immediately adjacent to said NKT cell epitope, or separated from said NKT cell epitope by a linker of at most 7 amino acids, and   (3) an optional flanking amino acid sequence of up to 10 amino acids at the N and/or C terminus of the peptide, wherein said antigenic protein does not comprise in its natural sequence a [C, S or T]-XX-C (SEQ ID NO: 19) or C-XX-[C, S or T] (SEQ ID NO: 18) motif within 11 amino acids N- or C terminally adjacent to said NKT cell epitope,   wherein X stands for any amino acid, and wherein said antigenic protein is not survivin.   
     
     
         18 . An in vitro method for obtaining a population of antigen-specific CD4+ NKT cells, the method comprising the steps of:
 contacting peripheral blood cells in vitro with an isolated immunogenic peptide; and   expanding said cells in the presence of IL-2, IL-15 or IL-7,   wherein the isolated immunogenic peptide comprises
 (1) a natural killer T (NKT) cell epitope having a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] (SEQ ID NO: 23) motif of an antigenic protein; 
 (2) a thioreductase [C, S or T]-XX-C (SEQ ID NO: 19) or C-XX-[C, S or T] (SEQ ID NO: 18) motif, which is either immediately adjacent to said NKT cell epitope, or separated from said NKT cell epitope by a linker of at most 7 amino acids, and 
 (3) an optional flanking amino acid sequence of up to 10 amino acids at the N and/or C terminus of the peptide, wherein said antigenic protein does not comprise in its natural sequence a [C, S or T]-XX-C (SEQ ID NO: 19) or C-XX-[C, S or T] (SEQ ID NO: 18) motif within 11 amino acids N- or C terminally adjacent to said NKT cell epitope, 
   wherein X stands for any amino acid, and wherein said antigenic protein is not survivin.   
     
     
         19 . The method according to  claim 18 , wherein the antigenic protein is selected from the group consisting of: a tumour associated antigenic protein, a viral protein, an autoantigen, an allofactor, an allergen, an alloantigen shed by a graft, an antigen of an intracellular pathogen, and an antigen from a viral vector used for gene therapy or gene vaccination. 
     
     
         20 . The method according to  claim 18 , wherein the natural killer T (NKT) cell epitope consists of 7 amino acids with a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] (SEQ ID NO: 23) motif of an antigenic protein. 
     
     
         21 . The method according to  claim 18 , wherein said NKT cell epitope has a [F or W]-XX-[I, L, M or V]-XX-[F or W] (SEQ ID NO: 13) motif. 
     
     
         22 . The method according to  claim 18 , wherein said thioreductase motif is C-XX-C (SEQ ID NO: 14). 
     
     
         23 . The method according to  claim 18 , wherein said antigenic protein is a multiple sclerosis autoantigen. 
     
     
         24 . The method according to  claim 18 , wherein said antigenic protein is myelin oligodendrocyte glycoprotein (MOG). 
     
     
         25 . The method according to  claim 18 , wherein said NKT cell epitope is FLRVPCWKI (SEQ ID NO: 38). 
     
     
         26 . The method according to  claim 18 , wherein the thioreductase motif is C-XX-C (SEQ ID NO: 14). 
     
     
         27 . A population of antigen-specific CD4+ NKT cells obtained by the method according to  claim 18 . 
     
     
         28 . A pharmaceutical composition comprising the population of antigen-specific CD4+ NKT cells obtained by the method according to  claim 18 . 
     
     
         29 . A method of treating a subject for a disease selected from the group consisting of: an infection with an intracellular pathogen, a tumour, an autoimmune disease, an immune response to an allofactor or to allergen exposure, an allograft rejection, and an immune response against a viral vector used for gene therapy or gene vaccination, comprising administrating a therapeutic amount of the population of antigen-specific CD4+ NKT cells obtained by the method according to  claim 18 .