Triple polypeptide complexes
AssigneeArexis AB
InventorsRikard Holmdahl, Jan Ake Engstrom, Jan Kihlberg, Harald Burkhardt
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Abstract
The invention provides methods and materials related to treating and diagnosing autoimmune conditions. Specifically, the invention provides polypeptide compositions, nucleic acids, substantially pure polypeptides, host cells, and methods for identifying a mammal with an autoimmune condition, treating a mammal with an autoimmune condition, and enhancing tolerance in a mammal with an autoimmune condition.
Claims71
A composition comprising three polypeptides, wherein each polypeptide comprises a triple helix formation sequence, wherein each polypeptide comprises at least two interpolypeptide linkages such that each polypeptide is covalently attached to at least one of the other two polypeptides of said three polypeptides, and wherein at least one of said interpolypeptide linkages comprises an Ahx-Lys bond.
A composition comprising three polypeptides, wherein each polypeptide comprises a triple helix formation sequence, wherein each polypeptide comprises at least one interpolypeptide linkage such that each polypeptide is attached to at least one of the other two polypeptides of said three polypeptides, and wherein at least one of said three polypeptides comprises an amino acid sequence at least about 80 percent identical to the sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 52, 53, 54, 55, or 56.
A composition comprising three polypeptides, wherein each polypeptide comprises a triple helix formation sequence, wherein each polypeptide comprises at least one interpolypeptide linkage such that each polypeptide is covalently attached to at least one of the other two polypeptides of said three polypeptides, and wherein at least one of said three polypeptides comprises a glycosylated amino acid residue.
A composition comprising three polypeptides, wherein each polypeptide comprises at least one interpolypeptide linkage such that each polypeptide is attached to at least one of the other two polypeptides of said three polypeptides, and wherein at least one polypeptide of said three polypeptides comprises (Gly-Pro-Flp).
A method for detecting an antibody in a sample from a mammal, wherein said antibody has specificity for a triple polypeptide complex, wherein said triple polypeptide complex comprises three polypeptides, wherein each of said three polypeptides comprises a triple helix formation sequence, wherein each of said three polypeptides comprises at least one interpolypeptide linkage such that each polypeptide is attached to at least one of the other two polypeptides of said three polypeptides, and wherein:
- (i) each polypeptide comprises at least two interpolypeptide linkages;
- (ii) at least one polypeptide of said three polypeptides comprises an amino acid sequence at least about 80 percent identical to the sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 52, 53, 54, 55, or 56;
- (iii) at least one polypeptide of said three polypeptides comprises a modified amino acid residue;
- or (iv) at least one polypeptide of said three polypeptides comprises (Gly-Pro-Flp),
- said method comprising:
- (a) contacting said sample with said triple polypeptide complex, and
- (b) determining the presence or absence of said antibody bound to said triple polypeptide complex, wherein the presence of bound antibody indicates that said sample contains said antibody.
A method for detecting a T-cell in a sample from a mammal, wherein said T-cell is reactive to a triple polypeptide complex, wherein said triple polypeptide complex comprises three polypeptides, wherein each of said three polypeptides comprises a triple helix formation sequence, wherein each of said three polypeptides comprises at least one interpolypeptide linkage such that each polypeptide is attached to at least one of the other two polypeptides of said three polypeptides, and wherein:
- (i) each polypeptide comprises at least two interpolypeptide linkages;
- (ii) at least one polypeptide of said three polypeptides comprises an amino acid sequence at least about 80 percent identical to the sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 52, 53, 54, 55, or 56;
- (iii) at least one polypeptide of said three polypeptides comprises a modified amino acid residue;
- or (iv) at least one polypeptide of said three polypeptides comprises (Gly-Pro-Flp),
- said method comprising:
- (a) contacting said sample with said triple polypeptide complex, and
- (b) determining the presence or absence of T-cell activation, wherein the presence of said T-cell activation indicates that said sample contains said T-cell.
A method of enhancing, in a mammal, tolerance to an endogenous polypeptide, said method comprising administering a composition to said mammal under conditions effective to enhance said tolerance, said composition comprising three polypeptides, wherein each of said three polypeptides comprises a triple helix formation sequence and at least one interpolypeptide linkage such that each of said three polypeptides is covalently attached to at least one of the other two polypeptides of said three polypeptides.
A method of forming, in a mammal, a triple helical polypeptide-antibody complex, said method comprising administering an antibody to said mammal under conditions effective to form said triple helical polypeptide-antibody complex with a triple helical polypeptide, said antibody having specificity for a triple polypeptide complex, wherein said triple polypeptide complex comprises three polypeptides, wherein each polypeptide comprises a triple helix formation sequence and at least one interpolypeptide linkage such that each polypeptide is attached to at least one of the other two polypeptides of said three polypeptides, and wherein at least one polypeptide of said three polypeptides comprises an amino acid sequence at least about 80 percent identical to the sequence set forth in SEQ ID NO:3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 52, 53, 54, 55, or 56.
A method of enhancing, in a mammal, tolerance to an endogenous polypeptide, said method comprising administering an isolated nucleic acid molecule to a somatic cell of said mammal under conditions effective to enhance said tolerance, wherein said nucleic acid molecule comprises a nucleic acid sequence that encodes a polypeptide comprising a triple helix formation sequence.
A method of enhancing, in a mammal, tolerance to an endogenous polypeptide, said method comprising administering cells to said mammal under conditions effective to enhance said tolerance, wherein said cells comprise an isolated nucleic acid molecule encoding a polypeptide comprising a triple helix formation sequence.
Dependencies are inferred from the claim text.