Ssx-2 peptide analogs

Abstract

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.

What is claimed is: 
     
         1 . An isolated peptide comprising one to three substitutions in the sequence KASEKIFYV (SEQ ID NO. 1), wherein the one to three substitutions are at amino acid position 1, 2, 4, 6, 8, or 9, wherein the peptide has an affinity for a class I MHC binding cleft that is similar to or greater than the affinity of KASEKIFYV (SEQ ID NO. 1) for said class I MHC binding cleft, wherein the one to three substitutions at amino acid position 1, 2, 4, 6, 8, or 9 are selected from the group consisting of:
 a substitution at position 1 with an aromatic amino acid or D-Lys,   a substitution at position 2 with a hydrophobic amino acid and/or an amino acid with a bulky side chain,   a substitution at position 4 with a polar amino acid,   a substitution at positions 6 with a polar amino acid, or an amino acid with a large aliphatic side chain,   a substitution at position 8 with a polar amino acid or an aromatic amino acid, and   a substitution at position 9 with a large aliphatic amino acid, and   wherein said isolated peptide is not a peptide of the sequence K{D-Ala}SEKIFYV or KASEKIFY{V—NH2}.   
     
     
         2 . The isolated peptide of  claim 1  wherein the halftime of dissociation is similar to or greater than the halftime of dissociation of KASEKIFYV (SEQ ID NO. 1) from said class I MHC binding cleft. 
     
     
         3 . The isolated peptide of  claim 1  that is recognized by T cells with specificity for the peptide KASEKIFYV (SEQ ID NO. 1). 
     
     
         4 . The isolated peptide of  claim 1 , wherein the peptide has affinity for a class I MHC peptide binding cleft. 
     
     
         5 . The isolated peptide of  claim 4 , wherein the class I MHC is HLA-A2. 
     
     
         6 . A class I MHC/peptide complex wherein the peptide has the sequence of the peptide of  claim 1  and is complexed with a MHC protein. 
     
     
         7 . The class I MHC/peptide complex of  claim 6 , that is cross-reactive with a TCR that recognizes a class I MHC/SSX-2 41-49  complex. 
     
     
         8 . The class I MHC/peptide complex of  claim 7 , wherein the class I MHC/SSX-2 41-49  complex is an HLA-A2/SSX-2 41-49  complex. 
     
     
         9 . A polypeptide comprising the peptide sequence of  claim 1 , in association with a liberation sequence. 
     
     
         10 . An immunogenic composition comprising the peptide of  claim 1 . 
     
     
         11 . An immunogenic composition comprising the polypeptide of  claim 9 . 
     
     
         12 . Nucleic acid means for expressing the peptide of  claim 1 . 
     
     
         13 . A nucleic acid encoding the polypeptide of  claim 9 . 
     
     
         14 . An immunogenic composition comprising the nucleic acid of  claim 12 . 
     
     
         15 . An immunogenic composition comprising the nucleic acid of  claim 13 . 
     
     
         16 . A method of inducing, maintaining, entraining, or amplifying a CTL response comprising intranodal administration of the composition of  claim 11 . 
     
     
         17 . A method of inducing, maintaining, entraining, or amplifying a CTL response comprising intranodal administration of the composition of  claim 10 . 
     
     
         18 . The method of  claim 17 , wherein the T cell response recognizes the native peptide. 
     
     
         19 . A method of inducing, maintaining, entraining, or amplifying a class I MHC-restricted T cell response comprising intranodal administration of the composition of  claim 11  plus an immunopotentiating agent. 
     
     
         20 . A method of inducing, maintaining, or entraining a CTL response comprising intranodal administration of the composition of  claim 14 .