Immunological IgE cross-reactions of bovine and human alpha-lactalbumins in cow's milk allergic patients

Despite great homology with the equivalent human protein, bovine alpha-lact albumin (B alpha-L alpha, a major component of whey, has been identified as a major milk allergen. The aim of this study was to investigate the relati onship between structure and IgE binding capacity in alpha-Las: (Ij the imp ortance of three-dimensional structure using native vs disulfide bridge-red uced B alpha-La; and (2) the incidence of amino acid sequence divergence on specific IgE cross-reactivity; to human vs bovine alpha-La. Purified nativ e, reduced and S-carboxymethylated B alpha-La and human alpha-La (H alpha-L A) were prepared. Specific IgE of 20 sera from patients with clinically rec ognized cow's milk protein allergy and positive RAST(R) rests to B alpha-La were measured in original direct and competitive ELISA inhibition tests. A ll sera containing specific anti-native B alpha-La IgE also reacted with de natured protein, but the IgE levels were generally lower; showing that thre e-dimensional structure is an important feature in B alpha-La allergenicity but that sequential epitopes are also exposed after protein denaturation. Despite lower IgE levels, all sera also gave significant IgE responses to H alpha-La. Competitive ELISA inhibition confirmed results obtained by direc t ELISA. The demonstrated IgE cross-reactivity between B alpha-LA and H alp ha-La could be related to the high degree of sequence homology between the two proteins but did not prove to have a clinical significance. However it is of great interest for a study of the relationship between structure, IgE binding capacity and allergenicity in alpha-Las.