Structure and function of milk allergens

Proteins (CMP) involved in milk allergy are numerous and heterogeneous, with very few structural or functional common features. This heterogeneity is complicated by their genetic polymorphism, resulting in several variants for each protein. These variants are characterized by point substitutions of amino acids or by deletions of peptide fragments of varying size or by post‐translational modifications such as phosphorylation or glycosylation. All of these modifications may affect allergenicity. No common molecular structure can be associated with allergenicity, although some homologous regions such as casein phospho‐peptides can explain an IgE cross‐reactivity. Three‐dimensional structure is an important feature in CMP allergenicity but denatured and linear epitopes are also involved. Epitopes are numerous and widely spread along the CMP molecule. They may be located in hydrophobic parts of the molecule where they are inaccessible for IgE antibodies in the native conformation of the protein but become bioavailable after digestive processes. Peptides as short as ca. 12–14 amino acid residues may account for a significant part of the allergenicity of the whole molecule, which justifies the need to be careful before proposing any CMP hydrolysate for highly allergenic children.