Identification of broadly reactive DR restricted epitopes

Abstract

The present invention is based on peptide binding specificities of HLA DRB1*0401, DR1 and DR7. Peptides binding to these DR molecules have a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, non charged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific secondary effects and secondary anchors are defined, and these results were utilized to derive allele specific algorithms. By the combined use of such algorithms peptides capable of degenerate DR1, 4, 7 binding were identified.

What is claimed is:  
     
         1 . A method for inducing or detecting a T-cell response, which comprises 
 (a) providing a peptide that bears a DR motif corresponding to a Class II HLA molecule;    (b) testing the peptide for binding affinity to a Class II HLA DR molecule, whereupon an IC 50  binding affinity is determined;    (c) comparing the binding affinity of the peptide to an IC 50  affinity threshold of 1,000 nM;    (d) identifying as a peptide suitable for administration as an immunogen a peptide that binds said Class II HLA DR molecule at a binding affinity of less than 1,000 nM; and    (e) contacting a Class II HLA DR molecule with a peptide identified by the steps (a) to (d), wherein a T-cell response is induced or detected.    
     
     
         2 . The method of  claim 1 , wherein the Class II HLA DR molecule is contacted with the peptide in an antigen presenting cell.  
     
     
         3 . The method of  claim 1 , wherein the Class II HLA DR molecule is contacted with the peptide ex vivo.  
     
     
         4 . The method of  claim 1 , wherein the class II HLA DR molecule is selected from the group consisting of DR1, DR2w2b, DR3w17, DR4w4, DR4w15, DR7, DR8w2, DR9, DR5w11, DR5w12, DR6w19, and DR2w2a.  
     
     
         5 . The method of  claim 2 , wherein the antigen presenting cell is a dendritic cell.  
     
     
         6 . The method of  claim 1 , wherein the motif consists of Y, F, W, L, I, V, or M in the first position and S, T, C, A, P, V, I, L, or M in the sixth position of a 9-residue core region of said peptide.  
     
     
         7 . The method of  claim 1 , wherein the peptide consists of a sequence selected from the group consisting of SEQ ID NO: 40-274.  
     
     
         8 . The method of  claim 1 , wherein the peptide is less than 50 amino acids in length.  
     
     
         9 . The method of  claim 8 , wherein the peptide is about 10 to about 30 amino acids in length.  
     
     
         10 . The method of  claim 9 , wherein the peptide is about 15 to about 20 amino acids in length.  
     
     
         11 . The method of  claim 1 , wherein the peptide is encoded by a nucleic acid.  
     
     
         12 . The method of  claim 2 , wherein the method further comprises contacting the antigen presenting cell with a second peptide, wherein the second peptide is capable of inducing a CTL response.  
     
     
         13 . The method of  claim 12 , wherein the second peptide is linked to the peptide that bears a motif corresponding to the class II HLA DR molecule.