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Possible role of anti-idiotypic antibodies in the induction of tumor immunity.

Introduction An idiotype (Id),' or idiotypic determinant, is the antigenic portion of an antibody that encompasses the variable (V) region of the molecule. Within the V region is the site where the antigen specifically binds to the antibody. Early studies by Oudin and Michel (1) and Kunkel and co-workers (2) indicated that an Id was unique to a small set of antibody molecules. However, Ids can also be shared by antibodies specific for a given antigen and are useful as phenotypic V region antibody gene markers (reviewed in references 3 and 4). The Id is often defined by an anti-idiotypic antibody (anti-Id), whereby the Id behaves as an antigen and induces the production of antibodies against itself. The idea that the immune response to an antigen can be regulated by a series of Id-anti-Id reactions was first proposed by Niels Jerne (5). This network theory of immune regulation proposes that Id-anti-Id reactions control a host's response to an antigen via either a positive (enhancing) or negative (suppressing) feedback mechanism. Id, located on or close to the antigen binding sites of both antibody molecules and lymphocyte antigen receptors, represent components of this network. Numerous studies have implicated Id networks in regulation of the immune response to a large variety of haptens and protein or carbohydrate antigens (reviewed in references 6 and 7). The injection of anti-Id before antigen exposure has resulted in either suppression of Id-positive antigen binding molecules or increased Id expression and antigen binding activity. Numerous reports have suggested the potential use of anti-Id in the induction of protective immunity against a wide variety of infectious agents (8-18). Thus, anti-Ids may represent possi-