Idiotype Network

Abstract

B‐lymphocytes have receptors, antibodies, with highly specific binding sites which bind to complementary structures. Receptors of a given cell have exactly one specific set of binding sites, the idiotype. Complementary structures can be found not only on antigen but also on antibodies of different idiotype or on T‐cell receptors. Thus a network of idiotypically interacting immune cells is formed, the idiotype network. The network influences the shaping of the B‐ and T‐cell repertoirs and may be relevant in the control of autoreactive clones. The therapeutic use of monoclonal antibodies against autoimmune diseases, cancer (in particular lymphoma) and a few other diseases relies on idiotypic interactions and is of rapidly growing importance. This strongly motivates further research to understand the systemic consequences of immunomanipulation.

Key Concepts:

  • An idiotope is a site on a B‐cell receptor that can bind to complementary structures; also on T‐cell receptors such sites exist.

  • The collection of idiotopes on one receptor is called idiotype; all receptors of a given cell have the same specific idiotype.

  • A huge diversity of idiotypes is generated by random somatic rearrangements of genes.

  • B‐cells of a given idiotype are stimulated to proliferate if its receptors are cross‐linked by complementary structures; unstimulated cells die.

  • Structures that bind to idiotopes can be found on antigen, not only on B or T cells of anti‐idiotype, but also on other cells or signalling molecules.

  • Immune cells, functionally connected by idiotypic interactions, form the idiotype network which influences the shaping of the B‐ and T‐cell repertoir and may be relevant in the control of autoreactive clones.

  • Therapeutic strategies using monoclonal antibodies rely on idiotypic interactions.

  • New technologies make extensive studies of the repertoir of immune receptors feasable, which are necessary to better understand the network properties and systemic consequences of immunomanipulation.

  • In many different fields the network paradigm has proved successful in describing complex systems, the recent progress in theoretical understanding should inspire further research on idiotype networks.

Keywords: idiotype; antibodies; antigens; B‐lymphocytes; T‐lymphocytes; autoimmunity; immunological memory; molecular mimicry; vaccination; network paradigm

Figure 1.

Antibody structure and molecular mimicry. (a) Schematic structure of an antibody with heavy and light chains, variable and constant regions, and idiotopes; the paratopes are marked by arrows. (b) Anti‐idiotypic antibodies may have idiotopes complementary to the paratope and is therefore similar to the antigen (mimicry), or they are complementary to antigen‐irrelevant idiotopes (no mimicry). Ab, antibody and Ag, antigen.

Figure 2.

Idiotypic interactions involving antibodies, antigen‐presenting cells (APCs) and T cells. (a) Interactions within the antibody network, (b) interactions involving antibodies and T cells and (c) interactions between T cells. See text for further detail. Ab, antibody; MHC, major histocompatibility complex and TCR, T‐cell receptor.

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Behn, Ulrich(Apr 2011) Idiotype Network. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000954.pub2]