Anti-Ids in Allergy: Timeliness of a Classic Concept

ABSTRACT: Anti-idiotypic antibodies (anti-ids) are part of natural immune responses with regulatory capacity. Their effect on an antigen-specific, so-called Ab1 antibody response, is dependent on 1) the original antigen, which they mirror, being Ab2 antibodies, and 2) their isotype. In the case of IgE-mediated allergy, natural anti-ids against allergen-specific IgE represent internal images of allergen molecules. A key biologic feature of allergens is that they can crosslink IgE, expressed by B-lymphocytes or passively bound via high affinity receptors to effector cells, which renders cellular activation. Therefore, the IgE cross linking capability of anti-ids determines whether they dampen or enhance immediate-type hypersensitivity. Correspondingly to classic antiallergen blocking IgG antibodies, anti-ids may also interact with inhibitory FcγRIIb receptors and, thereby, down-regulate T(H)2-type inflammation. Anti-ids and other B-cell epitope mimetics, like mimotopes and DARPins, represent antigen surrogates, which can be used for vaccination. Intriguingly, they may induce antibody responses without activating potentially proinflammatory, antiallergen T-lymphocytes. Taken together, collective evidence suggests that anti-ids, although representing immunologic classics, are a timeless concept in allergology.