Heteroclitic analogs and related methods
Heteroclitic analogs of Class I epitopes are prepared by providing conservative or semi-conservative amino acid substitutions at positions 3 and/or 5 and/or 7 of these epitopes. The analogs are useful in eliciting immune responses with respect to the corresponding wildtype epitopes.
1 - 11 . (canceled)
12 . A peptide comprising an analog of a Major Histocompatibility Complex (MHC) class I peptide epitope, wherein said analog has enhanced immunogenicity compared to said epitope, and wherein said peptide analog is prepared by:
a) identifying a MHC class I epitope comprising a formula (A), wherein formula (A) is Rn-R2-R3-R4-R5-R6-R7- . . . Rx,
Rn is the N-terminal amino acid,
Rx is the C-terminal amino acid,
x=8-11 such that Rx can be from the eighth to the eleventh amino acid residue from Rn,
R2 or R3 and Rx are primary anchor residues of a motif or supermotif, and
b) producing a polypeptide comprising an analog, said analog comprising a formula (B) identical to said formula (A) except one or more conservative or semiconservative amino acid substitutions at R3 and/or R5 and/or R7, provided said one or more substitutions is not of a primary anchor residue.
13 - 15 . (canceled)
16 . A composition comprising at least the peptide of claim 12 .
17 . The composition of claim 16 , wherein the peptide contains 9-15 amino acids.
18 . The composition of claim 16 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19 and SEQ ID NO:20.
19 . A composition of claim 16 , wherein the peptide is admixed or joined to a CTL epitope.
20 . A composition of claim 16 , wherein the peptide is admixed or joined to an HTL epitope.
21 . A composition of claim 20 , wherein the HTL epitope is a pan-DR binding molecule.
22 . A composition of claim 16 , further comprising a liposome.
23 . A composition of claim 16 , wherein the epitope is coupled to a lipid.
24 . A composition of claim 16 , wherein said epitope is included in a heteropolymer.
25 . A composition of claim 16 , wherein the epitope is included in a homopolymer.
26 - 30 . (canceled)
31 . The composition of claim 16 , further comprising a label.
32 . The composition of claim 31 , wherein the label is biotin, a fluorescent moiety, a non-mammalian sugar, a radio label or a small molecule to which a monoclonal antibody binds.
33 . The composition of claim 16 which is a vaccine containing:
a unit dosage of said peptide, and
a pharmaceutical excipient.
34 - 39 . (canceled)