Oral Tolerance Induced by Gut-Processed Antigen

Abstract

Different mechanisms operate to produce the suppression of humoral and cellular immune responses after feeding protein antigen to mice (1). In experiments designed to examine the role of the gut in “processing” of fed antigen, (ovalbumin, OVA), we found that serum collected one hour after feeding and administered intraperitoneally into naive recipients transferred tolerance for CMI but not for antibody responses (2). We postulated that in the time between feeding and collection of serum, OVA had been processed by the gut, and converted from immunogenic into tolerogenic forms. Further experiments are now reported, in which we have investigated the relevance of systemic as opposed to gut antigen processing by using a biological filtration experiment similar to that used by others in the investigation of macrophage function (3,4). We attempted to mimic physicochemical alteration to the native protein by injecting mice with a range of doses of native, deaggregated and urea-denatured OVA. The relevance of epitopes recognized by anti-OVA antibody has been studied by immunoabsorption of tolerogenic serum and, finally, the size of the tolerogen has been estimated by transfer of fractions of serum, separated on the basis of molecular weight.