Anti-TSH anti-idiotypic antibodies : characteristics and applications

Briones-Urbina, Rosario (1987) Anti-TSH anti-idiotypic antibodies : characteristics and applications. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Antibody combining sites represent mirror images of their antigen epitopes. Anti-idiotypic antibodies specific for the combining site for the first antibody could exhibit similar tridimentional structure to that of the original epitope. With this background, internal image anti-idiotypic antibodies have been tested by numerous groups of investigators in several biological systems. Some of these were without any specific biological activity but others such as anti-insulin, anti-acetylcholine and anti-beta adrenergic receptor agonists have been found to have agonistic activity at the level of their specific receptors. -- Graves' Disease is an autoimmune disorder involving the thyroid gland. Its etiological agent is thought to be an antibody with agonistic properties at the level of the thyroid stimulating hormone (TSH) receptor. The receptor itself has been thought to be the antigen responsible for the production of this antibody. However, considering the above mentioned premises, it is possible to speculate that the thyroid stimulating antibody of Graves' Disease could, at least in some cases, be an anti-TSH anti-idiotypic antibody. -- This work was designed to investigate the possibility of producing anti-TSH anti-idiotypic antibodies and to test their biological activities. Anti-TSH antibodies were raised by injecting rats with highly purified TSH. This first antibody was later purified and used in the production of anti-idiotypic antibodies this time in rabbits. The activity of the anti-TSH anti-idiotypic antibodies was tested in experiments in vitro. It was demonstrated that the antibodies produced were true agonists at the TSH receptor level. They were capable of interfering with the binding of TSH to its receptor, activating adenylate cyclase, promoting adenylate cyclase mediated cellular processes and recognizing the TSH receptor protein in thyroid plasma membrane protein blots. -- A second group of experiments explored the activity of anti-idiotypic antibodies directed to the individual subunits of the TSH molecule. The information obtained appears to favour different requirements for receptor binding and postbinding events. Antibodies with activity specific for each of the subunits of TSH were individually capable of binding to thyroid plasma membranes. On the contrary, there was absolute requirement for the participation of both antibodies for the activation of adenylate cyclase. -- The third part of this work explores the influence that TSH may have on the synthesis and turnover of its receptor. These experiments were possible thanks to a detection system that benefits from the capacity of anti-TSH in the regulation of receptor synthesis and turnover. TSH accelerates the synthesis and prolongs the half life of its own receptor. -- In summary this work has demonstrated that it is possible to raise anti-TSH anti-idiotypic antibodies. The antibodies produced had agonistic effects at the level of the TSH receptor. It was also shown that these antibodies can be useful tools in the detection of receptor proteins and in the investigation of the hormone-receptor interaction.

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