T-cell death-inducing epitopes
Cell death-inducing epitopes and polypeptides containing same. Also disclosed are compounds for inducing death of activated T-cells, a method of producing antibodies to the epitopes, a method of identifying compounds that bind to the epitopes, a method of inducing death of activated T-cells, and pharmaceutical compositions containing the compounds.
1 . A three-dimensional conformation of an isolated epitope represented by X 1 -X 2 -X 3 -X 4 -X 5 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and
X 1 is Tyr, Trp, His, or Met;
X 2 is Asp;
X 3 is Ser, Phe, Pro, Glu, or His;
X 4 is any amino acid; and
X 5 is Pro, Tyr, His, or Trp.
2 . An isolated polypeptide comprising X 1 -X 2 -X 3 -X 4 -X 5 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and
X 1 is Tyr, Trp, His, or Met;
X 2 is Asp;
X 3 is Ser, Phe, Pro, Glu, or His;
X 4 is any amino acid; and
X 5 is Pro, Tyr, His, or Trp.
3 . The polypeptide of claim 2 , wherein the polypeptide is 5 to 1500 amino acids in length.
4 . The polypeptide of claim 3 , wherein the polypeptide is 5 to 150 amino acids in length.
5 . The polypeptide of claim 4 , wherein the polypeptide is 5 to 15 amino acids in length.
6 . The polypeptide of claim 2 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs:4 and 6-13.
7 . The polypeptide of claim 2 , wherein the polypeptide is X 1 -X 2 -X 3 -X 4 -X 5 .
8 . An antibody that binds to an epitope having the three-dimensional conformation of claim 1 and induces death of activated T-cells.
9 . The antibody of claim 8 , wherein the antibody is monoclonal.
10 . A three-dimensional conformation of an isolated epitope represented by X 6 -X 7 -X 8 -X 9 -X 10 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and
X 6 is Asp;
X 7 is Tyr, Met, Asn, Trp, or Phe;
X 8 is Phe or Leu;
X 9 is Pro; and
X 10 is Glu.
11 . An isolated polypeptide comprising X 6 -X 7 -X 8 -X 9 -X 10 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and
X 6 is Asp;
X 7 is Tyr, Met, Asn, Trp, or Phe;
X 8 is Phe or Leu;
X 9 is Pro; and
X 10 is Glu.
12 . The polypeptide of claim 11 , wherein the polypeptide is 5 to 1500 amino acids in length.
13 . The polypeptide of claim 12 , wherein the polypeptide is 5 to 150 amino acids in length.
14 . The polypeptide of claim 13 , wherein the polypeptide is 5 to 15 amino acids in length.
15 . The polypeptide of claim 11 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs:14-18.
16 . The polypeptide of claim 11 , wherein the polypeptide is X 6 -X 7 -X 8 -X 9 -X 10 .
17 . An antibody that binds to an epitope having the three-dimensional conformation of claim 10 and induces death of activated T-cells.
18 . The antibody of claim 17 , wherein the antibody is monoclonal.
19 . A three-dimensional conformation of an isolated epitope represented by X 11 -X 12 -X 13 -X 14 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and
X 11 is Pro;
X 12 is Met;
X 13 is Glu or Ser; and
X 14 is Ile.
20 . An isolated polypeptide comprising X 11 -X 12 -X 13 -X 14 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and
X 11 is Pro;
X 12 is Met;
X 13 is Glu or Ser; and
X 14 is Ile.
21 . The polypeptide of claim 20 , wherein the polypeptide is 4 to 1500 amino acids in length.
22 . The polypeptide of claim 21 , wherein the polypeptide is 4 to 150 amino acids in length.
23 . The polypeptide of claim 22 , wherein the polypeptide is 4 to 15 amino acids in length.
24 . The polypeptide of claim 20 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs: 20-22.
25 . The polypeptide of claim 20 , wherein the polypeptide is X 11 -X 12 -X 13 -X 14 .
26 . An antibody that binds to an epitope having the three-dimensional conformation of claim 19 and induces death of activated T-cells.
27 . The antibody of claim 26 , wherein the antibody is monoclonal.