Immunoregulatory effects of a covalent antigen–antibody complex

Abstract

It is becoming increasingly clear that any specific immune response must be subject to a control mechanism of the same order of specificity. The basis of such specificity in control almost certainly lies in the antibodies themselves, whether free or cell bound. The response to a given antigen might then be regulated by antibodies specific either for the antigen (‘Ab 1’) or for the variable regions (idiotypes) of Ab 1. Whereas the latter can interact directly with the binding sites of cellular receptors for antigen, the former can only do so if the antigen is also present to act as a bridge. Furthermore, because an anti-idiotype antiserum is usually prepared against a monoclonal antibody, it will only be able to influence directly those clones of cells which carry the chosen idiotype, and thus may leave unaffected other clones which are specific for the same antigen but which carry different idiotypes. An immune complex, on the other hand, should influence all clones sensitive to the antigen in question. Experimentally, the injection of antigen–antibody complexes can either increase^1,2 or decrease^3,4 the subsequent response to antigen. These effects often require the presence of an intact Fc region⁴ and may differ according to the class (or isotype) of the antibody⁵. The injection of anti-idiotype antisera can have striking effects on the expression of particular idiotypes, but usually has little effect on the overall response. Again, these effects require the participation of the Fc region of the anti-idiotype antibody⁶, and can vary according to its isotype^7,8. To study the regulatory effects of antibody more closely, we have attempted to prepare immune complexes which could influence the overall response, and yet have effects as powerful as those obtained with anti-idiotype antibodies. The immune complexes obtained were of the defined constitution Ag₂Ab, in which stability was ensured by linking antigen to antibody through a covalent bond. We report here that, depending on the conditions used, these complexes induced either priming or tolerance of the response of mice towards subsequent injections of antigen alone. We consider that such complexes could be useful not only as tool for studying immunoregulation, but also as a practical means of influencing immune responses.