What Is an Anti-idiotypic Antibody?

Posted by Jerry Carter on January 16th, 2019

An anti-idiotypic antibody is an antibody that specifically binds to the antigen binding site of another antibody, typically a humanized antibody. In the term of the “anti-idiotypic antibody”, the “idiotype” represents a characteristic shared by a panel of immunoglobulin or T cell receptor (TCR) molecules based on the antigen binding specificity and structure of their variable region. Anti-idiotypic antibodies play a huge role in biomedical research. In contrast with the therapeutic agonistic antibody, the anti-idiotypic antibody is made use of in preclinical practices for pharmacokinetic analysis, or it can serve as control groups, employed for immunogenicity assays. Then, how the anti-idiotypic antibody got its name and what types do they have? The two questions are to be replied below.

In 1963, scientists represented by Oudin immunized 50 rabbits with typhoid salmonella, used the anti-typhoid salmonella antibody isolated from the serum of one of the rabbits as the immunogen to immunize normal rabbits, and finally obtained the anti-antibody by isolating its serum. As a result, this anti-antibody was found only reacting with the antityphoid shigella antibody which functions as an immunogen, but not being able to precipitate with the serum of the remaining 49 rabbits immunized with salmonella typhi, nor can it react with the serum of other antigens immunized rabbits or normal rabbits. The result indicates that the antityphoid antibody derived from the rabbit of interest contains a specific epitope, which is different from the antigens produced by other rabbits against the same antigen (typhoid salmonella) or the antigens generated by the same rabbit against different antigens. Since the antigen-determining cluster differs from isotype or allotype, Oudin named it as “idiotype”, meaning “individual genetic type.” That is how the anti-idiotypic antibody got its name.

According to how these antibodies bind to the target, anti-idiotypic antibodies are usually divided into three major types. The first type is an antigen blocking anti-idiotypic antibody, named so because the targeting antibody’s paratope and idiotope overlap with each other. Due to this reason, the antibody drug’s target antigen and the anti-idiotypic antibody will vie for the same epitope-specific site. Thus, this type of anti-idiotypic antibody can only be used to detect free antibody drugs. The second class is called non-blocking because the antibody drug’s paratope and idiotope never overlap, indicating the anti-idiotypic antibody and the antigen can simultaneously bind to the antibody drug without inhibiting the binding capability of either of them. That’s why non-blocking anti-idiotypic antibodies are utilized to test the presence of all kinds of available antibody drugs (free or antigen bound). The third type of anti-idiotypic antibody is a complex specific anti-idiotypic antibody. Such an antibody cannot bind to the antibody drug unless the drug is already bound to its antigen. Therefore, this type has only been applied to the detection of bound antibody drugs.

Given their unique physical structure and chemical nature, anti-idiotypic antibodies will continue to contribute to pharmacokinetic research. Moreover, with the development of the medical science, people will gain a better understanding of anti-idiotypic antibodies, which are going to be optimized further to play more roles.

About Creative Biolabs

Creative Biolabs is a leading custom service provider, boasting abundant experience in antibody generation and engineering. Its service portfolio involves Murine, human, monkey, rabbit, chicken, dog, llama and camel monoclonal antibody production. Moreover, the company also conducts in-depth antibody humanization and affinity maturation by means of phage display and DNA mutagenesis approaches.