Heteroclitic analogs and related methods

Abstract

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)