It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (
T cell) binding sites, can be modified to be less allergenic by modifying the
IgE binding sites. The
IgE binding sites can be converted to non-
IgE binding sites by masking the site with a compound that prevents IgE binding or by altering as little as a
single amino acid within the
protein, most typically a
hydrophobic residue towards the center of the IgE-binding
epitope, to eliminate IgE binding. The method allows the
protein to be altered as minimally as possible, other than-within the IgE-binding sites, while retaining the ability of the
protein to activate T cells, and, in some embodiments by not significantly altering or decreasing
IgG binding capacity The examples use peanut allergens to demonstrate alteration of IgE binding sites. The critical amino acids within each of the
IgE binding epitopes of the peanut protein that are important to
immunoglobulin binding have been determined. Substitution of even a
single amino acid within each of the epitopes led to loss of IgE binding. Although the epitopes shared no common
amino acid sequence motif, the hydrophobic residues located in the center of the
epitope appeared to be most critical to IgE binding.