Role of antigen structure in the regulation of IgE isotype expression.

Tobacco glycoprotein (TGP) is a glycoprotein containing rutin-like polyphenol groups that is purified from cured tobacco leaves and can be detected in condensates of tobacco smoke. One-third of normal humans have been shown to manifest immediate, IgE-mediated, wheal and flare reactions to an intradermal injection of TGP. Rutin-like moieties are also found in a wide variety of vegetable foods. The possible importance of sensitivity to TGP in the pathogenesis of the vascular and pulmonary complications of tobacco smoking has stimulated us to study the immune response of mice to TGP and the role of rutin groups in influencing isotype expression. A series of three intradermal injections of TGP elicits a long-lasting IgE antibody response in mice. However, no hemagglutinating antibodies are produced. Similarly, immunization with a rutin derivative of bovine serum albumin stimulates IgE antibodies to bovine serum albumin but little hemagglutinating antibodies. In contrast, mice injected in the same manner with bovine serum albumin produce both IgE and hemagglutinating antibodies. Thus, the rutin moiety is implicated as exerting a regulatory effect on isotype expression by suppressing the production of serum antibodies of isotypes other than IgE. The immunization procedure employed (which involves an initial injection of 100 micrograms of antigen in phosphate-buffered saline, followed, at monthly intervals, by two intradermal injections of 100 micrograms of antigen precipitated on alum) apparently fails to stimulate the normal "down-regulation" of the IgE response so that a persisting high-titered response is obtained.