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Idiotopes

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In immunology, an idiotope is the unique set of antigenic determinants (epitopes) of the variable portion of an antibody.[1] In some cases it can be the actual antigen-binding site, and in some cases it may comprise variable region sequences outside of the antigen-binding site on the antibody itself. Thus each antibody would have multiple idiotopes; and the set of these individual idiotopes is termed the idiotype of the antibody.

Idiotopes contrast with allotopes, which are non-varying structures on the Fc receptor.[1]

If a separate antibody is produced that has specific binding capabilities to an idiotope of the previously described antibody, it is said to be an "anti-idiotypic antibody". If such is the case, the anti-idiotypic antibodies will be able to bind to the B lymphocyte receptor for the original antigen and inhibit the immune response to that antigen.[2]

This type of regulation was proposed by Danish immunologist Niels Jerne in 1974. He termed it the "Network Hypothesis". This type of B lymphocyte regulation may be partially responsible for preventing an immune response from getting out of control, which would elicit damage to host tissue or even cause an autoimmune diseased state.

Because of the resemblance of anti-idiotypic antibodies to the original antigen, vaccine studies have been performed.[3] These types of vaccines are called "idiotypic vaccines". An anti-idiotypic monoclonal antibody was generated to possess an "internal image of cocaine".[4] The anti-idiotypic antibody bound to the human dopamine transporter with mimicry of the cocaine molecule and completely inhibited cocaine binding.[5] None are produced commercially to date.

References

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  1. ^ a b "Dorlands Medical Dictionary". Retrieved 2008-03-23.
  2. ^ "How Anti-Idiotypic Antibodies are Essential to Drug Discovery". News & Blogs. GenScript Biotech. January 19, 2018. Retrieved 2021-12-29.
  3. ^ Ladjemi MZ (2012). "Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements". Front Oncol. 2: 158. doi:10.3389/fonc.2012.00158. PMC 3490135. PMID 23133825.
  4. ^ Ho, Mitchell; Segre, Mariangela (2003-07-30). "Inhibition of cocaine binding to the human dopamine transporter by a single chain anti-idiotypic antibody: its cloning, expression, and functional properties". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1638 (3): 257–266. doi:10.1016/s0925-4439(03)00091-7. ISSN 0006-3002. PMC 3295240. PMID 12878327.
  5. ^ Ho, Mitchell; Segre, Mariangela (July 2000). "Dopamine uptake by mouse neuroblastoma N1E-115 cells stably expressing human dopamine transporter is differentially inhibited by anti-idiotypic Ab2β antibodies mimicking the configuration of cocaine". Brain Research. 872 (1–2): 231–235. doi:10.1016/S0006-8993(00)02491-4. PMID 10924700. S2CID 23356539.