Identification of broadly reactive DR restricted epitopes
OwnerAlessandro Sette, John Sidney +1inventors
InventorsAlessandro Sette, John Sidney, Scott Southwood
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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.
Claims13
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 IC50 binding affinity is determined;
- (c) comparing the binding affinity of the peptide to an IC50 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.
Dependencies are inferred from the claim text.