Chemical Denaturation of Ovalbumin Abrogates the Induction of Oral Tolerance of Mouse Reaginic Antibody Responses

The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4) and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although denatured OVA is hypoallergenic, the present result indicates that denaturation of a soluble protein prevents the induction of oral tolerance of Th2 responses.