Antiidiotype

An antiidiotype is an antibody that binds to the idiotype—the unique antigen-binding region—of another antibody, thereby potentially interfering with antigen recognition. The concept is central to the idiotype–anti-idiotype network theory, proposed by Niels Jerne, which posits that antibodies regulate immune responses through a cascade of anti-idiotypic and anti-anti-idiotypic antibodies, forming a regulatory network.

Anti-idiotype antibodies (Ab2) may neutralize the stimulation provided by the original antibody by occupying its binding site. Alternatively, many Ab2 antibodies can mimic the three-dimensional shape of the original antigen’s epitope; such antibodies are said to carry an internal image of the antigen and can act as surrogate antigens that elicit immune responses without exposure to the actual antigen.

Physiologically, anti-idiotype interactions contribute to immune regulation, tolerance, and possibly autoimmunity when networks are perturbed. They have been explored in vaccine design and cancer immunotherapy, where anti-idiotype antibodies are used to induce or modulate antibodies against a target epitope by presenting a mimicry rather than the real antigen. They also provide a tool to study antibody repertoires and B cell regulation.

Not all anti-idiotypic interactions lead to useful outcomes; some are inconsequential or redundant, and the network is complex and context-dependent.