PSMA peptide analogues
Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally, classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.
1. An isolated peptide consisting essentially of the sequence P0-P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11, in which:
P0 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid; and
P1 is G; and
P2 is L; and
P3 is P; and
P4 is S; and
P5 is I; and
P6 is P; and
P7 is V; and
P8 is H; and
P9 is P; and
P10 is L, Nva, or Nle; and
P11 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid.
2. An isolated peptide consisting essentially of the sequence:
GLPSIPVHPL;
(SEQ ID NO. 365)
or
GLPSIPVHP{NVa};
(SEQ ID NO. 366)
or
GLPSIPVHP{Nle}
(SEQ ID NO. 367).
3. An isolated peptide consisting essentially of the sequence:
GLPSIPVHP{Nva} (SEQ ID NO. 366).
4. A class I MHC-peptide complex wherein the peptide has the sequence of the peptide of claim 1 .
5. A polypeptide comprising the peptide sequence of claim 1 embedded within a liberation sequence.
6. An composition comprising the peptide of claim 1 .
7. An composition comprising the polypeptide of claim 5 .
8. A nucleic acid encoding the polypeptide of claim 5 .
9. A nucleic acid means for expressing the peptide of claim 1 .
10. An immunogenic composition comprising the nucleic acid of claim 8 or 9 .
11. A method of inducing, maintaining, or amplifying a CTL response in a mammal comprising intranodal administration of the composition of claim 6 .
12. A method of entraining a class I MHC-restricted T cell response in a mammal comprising intranodal administration of the composition of claim 6 and an immunopotentiating agent.
13. A method of inducing, maintaining, or entraining a CTL response in a mammal comprising intranodal administration of the composition of claim 10 .
14. The isolated peptide of claim 2 consisting essentially of the sequence: GLPSIPVHPL (SEQ ID NO. 365).
15. The isolated peptide of claim 2 consisting essentially of the sequence: GLPSIPVHP{Nle}(SEQ ID NO. 367).
16. An isolated peptide comprising the sequence:
GLPSIPVHPL;
(SEQ ID NO. 365)
or
GLPSIPVHP{NVa};
(SEQ ID NO. 366)
or
GLPSIPVHP{Nle}
(SEQ ID NO. 367).
17. The isolated peptide of claim 16 comprising the sequence: GLPSIPVHPL (SEQ ID NO. 365).
18. The isolated peptide of claim 16 comprising the sequence:
GLPSIPVHP{Nva} (SEQ ID NO. 366).
19. The isolated peptide of claim 16 comprising the sequence:
GLPSIPVHP{Nle} (SEQ ID NO. 367).
20. An isolated peptide consisting of the sequence P0-P1-P2-P3-P4-P5-P6-P7-P8-P9-P10, in which:
P0 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid; and
P1 is G; and
P2 is L; and
P3 is P; and
P4 is S; and
P5 is I; and
P6 is P; and
P7 is V; and
P8 is H; and
P9 is P; and
P10 is L, Nva, or Nle; and
P11 is X, XX, or XXX, wherein X specifies any amino acid or no amino acid.
21. The isolated peptide of claim 16 or 20 consisting of the sequence:
GLPSIPVHPL;
(SEQ ID NO. 365)
or
GLPSIPVHP{NVa};
(SEQ ID NO. 366)
or
GLPSIPVHP{Nle}
(SEQ ID NO. 367).
22. The isolated peptide of claim 21 consisting of the sequence:
GLPSIPVHPL (SEQ ID NO. 365).
23. The isolated peptide of claim 21 consisting of the sequence: GLPSIPVFIP{Nva}(SEQ ID NO. 366).
24. The isolated peptide of claim 21 consisting of the sequence: GLPSIPVHP{Nle}(SEQ ID NO. 367).
25. A class I MHC-peptide complex, wherein the peptide has the sequence of the peptide of claim 16 or 20 .
26. A polypeptide comprising the peptide sequence of claim 16 or 20 embedded within a liberation sequence.
27. An composition comprising the peptide of claim 16 or 20 .
28. A nucleic acid encoding the polypeptide of claim 26 .
29. A nucleic acid means for expressing the peptide of claim 26 or 20 .
30. An composition comprising the nucleic acid of claim 28 or 29 .
31. A method of inducing, maintaining, or amplifying a CTL response in a mammal comprising intranodal administration of the composition of claim 27 .
32. A method of entraining a class I MHC-restricted T cell response in a mammal comprising intranodal administration of the composition of claim 27 and animmunopotentiating agent.
33. A method of inducing, maintaining, or entraining a CTL response in a mammal comprising intranodal administration of the composition of claim 30 .