RETRO - INVERSO REGULATORY T CELL EPITOPES
The present disclosure provides retro-inverso Tregitope compounds and compositions as well as methods for their preparation and use.
1 - 79 . (canceled)
80 . A composition comprising:
a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-29 and 42-107, and/or fragments and variants thereof, and optionally 1 to 12 additional amino acids distributed in any ratio on the N terminus and/or C-terminus of the polypeptide of SEQ ID NOS: 1-29 and 42-107, wherein each of the amino acids of SEQ ID NOS: 1-29 and 42-107, and optionally the extensions thereof, except for glycine are in the D-amino acid configuration,
a nucleic acid encoding said polypeptide, or
a vector comprising said nucleic acid, or
a cell comprising said vector.
81 . The composition of claim 80 , further comprising one or more immune stimulating T-cell epitope polypeptides.
82 . The composition according to claim 81 , wherein said one or more immune stimulating T-cell epitope polypeptides is one or more therapeutic protein, treatment with a vaccine or treatment with at least one antigen.
83 . The composition according to claim 80 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 16.
84 . The composition according to claim 80 , wherein each of the amino acids of said SEQ ID NOS: 1-29 and 42-107, and optionally the extensions thereof, except for glycine are in the D-amino acid configuration.
85 . The composition of claim 84 , wherein said polypeptide is linked to a heterologous polypeptide.
86 . The composition of claim 85 , wherein the retro-inverso T-cell polypeptide is fused to the N-terminus of the heterologous polypeptide.
87 . The composition of claim 85 , wherein the retro-inverso T-cell polypeptide is fused to the C-terminus of the heterologous polypeptide.
88 . The polypeptide composition of claim 85 , wherein the heterologous polypeptide comprises a biologically active molecule and wherein the biologically active molecule is selected from the group consisting of an immunogenic molecule, a T-cell epitope, a viral protein, and a bacterial protein.
89 . The composition of claim 88 , wherein said immunogenic molecule is antigens and/or allergens.
90 . The composition of claim 80 , wherein said polypeptide comprises SEQ ID NO: 1 or SEQ ID NO: 16.
91 . A method for inducing suppression of an immune response in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 80 .
92 . The method according to claim 91 , wherein the immune response is a result of treatment with at least one or more therapeutic treatments with at least one therapeutic protein, treatment with a vaccine or treatment with at least one antigen.
93 . The method according to claim 91 , wherein said polypeptide is administered to isolated dendritic cells ex vivo, and said dendritic cells are the re-introduced to the subject.
94 . The method according to claim 91 , wherein the administration shifts one or more antigen presenting cells or dendritic cells to a regulatory phenotype.
95 . The method according to claim 94 , wherein the regulatory phenotype is characterized by a decrease in CD11c and HLA-DR expression in the dendritic cells or antigen presenting cells.
96 . The method according to claim 91 , wherein the administration shifts one or more T cells to a regulatory phenotype.
97 . The method according to claim 96 , wherein the administration epitope shifts one or more CD4+ T-cells or CE8+ T-cells to a regulatory phenotype.
98 . The method according to claim 91 , wherein the administration shifts one or more B cells to a regulatory phenotype.
99 . The method according to claim 91 , wherein the administration activates CD4 + /CD25 + /FoxP3 + regulatory T-cells.
100 . The method of claim 91 , wherein the administration suppresses an immune response selected from the group consisting of an innate immune response, an adaptive immune response, an effector T-cell response, a memory T-cell response, a helper T-cell response, a B-cell response, a ηKT-cell response, or any combination thereof.