Immunogenic peptides and their use in immune disorders
View Patent ↗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 recognized by a CD4+ T cell, more specifically, of an allergen or autoantigen, 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 may be used for the prevention or treatment of immune disorders, more specifically, of allergic disorders or autoimmune diseases. The present invention thus provides methods of treatment or preventing immune disorders by using such peptides.
1. A method of eliciting cytolytic CD4+ T cell activity in an individual, comprising administering to said individual an isolated immunogenic peptide with a length of at most 75 amino acids, derived from an autoantigenic protein involved in an autoimmune disease, wherein said immunogenic peptide comprises a T cell epitope sequence of said autoantigenic protein and a sequence with the motif C—(X)2-C, said sequence with the motif being either adjacent to said epitope sequence, or separated from said epitope sequence by a linker of at most 7 amino acids.
2. The method according to claim 1 , wherein said motif does not naturally occur within a region of 11 amino acids N-terminally or C-terminally of the T-cell epitope in said protein.
3. The method according to claim 1 , wherein said immunogenic peptide sequence has a length of between 12 and 19 amino acids.
4. The method according to claim 1 , said sequence with the motif being either adjacent to said epitope sequence, or separated from said epitope sequence by a linker of at most 4 amino acids.
5. The method according to claim 1 , wherein said immunogenic peptide sequence has a length of up to 50 amino acids.
6. The method according to claim 1 , wherein said immunogenic peptide sequence has a length of up to 30 amino acids.
7. The method according to claim 1 , wherein said autoantigen 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.