Idiotypes

Abstract

Idiotypes are unique determinants of an immunoglobulin or T‐cell receptor that can function as antigens. Responses to idiotypes, which include anti‐idiotypic (Id) antibody (Ab)‐producing B cells and idiotype‐specific T cells, form a network that regulates their production, referred to as the idiotypic network. In an immune response, antibody 1 (Ab1) is produced in response to an antigen, and anti‐Id Ab produced to Ab1 (Ab2) may bind in the antigen‐combining site (Ab2β) or the framework region (Ab2γ) of Ab1. As Ab2β can fit in the paratope of an antigen receptor of B or T cells, it mimics the three‐dimensional structure and is the internal image of antigen, and has the potential to activate Ab1 precursors reactive with the antigen. These findings have led to the use of Ab2β as an immunogen to elicit specific immune responses to foreign pathogens, as probes to study cell surface receptors and as immune therapy for tumours.

Key Concepts:

  • Idiotypes are unique determinants located in the variable region of antigen receptors on B cells (immunoglobulin, Ig) and T cells (T‐cell receptor, TCR).

  • Antibody 1 (Ab1) is produced in response to an antigen and Ab2 produced to Ab1 may react with the antigen‐combining site (Ab2β, internal image of antigen) or the framework region (AB2γ) of the antibody molecule.

  • The interaction of clones of B and T cells that express distinct idiotypic specificities to regulate the immune response is referred to as the idiotypic network.

  • The idiotypic network can be exploited to elicit specific immune responses to foreign pathogens, to study cell surface receptors and as immune therapy for tumours.

Keywords: idiotype; idiotypic network; Jerne; antiidiotype

Figure 1.

An antigenic epitope (x) is processed and presented by an antigen‐presenting cell (APC) in association with Class II MHC to an antigen‐specific T‐helper cell or, in association with Class I MHC, to an antigen‐specific cytotoxic T cell. Signals from the T‐helper cell lead to the activation of B cells that produce antiepitope x antibody (Ab1), which will express idiotype y. Anti‐x producing B cells, as APCs, present idiotypic peptide y in association with Class II to idiotype y‐reactive or specific T‐helper cell and, in association with Class I, to idiotype y‐specific cytotoxic T cells. Signals from the activated idiotype y‐reactive T cells lead to the activation of antiidiotope y‐producing B cells (Ab2). Dendritic cells may also present idiotypic peptides to T cells.

Figure 2.

Idiotypic cascade. A foreign antigenic epitope (x) induces an immune response characterized by the production of Ab1 antibody, which is anti‐x and contains several idiotopes, which can either be paratopic or nonparatopic (framework). Ab1 can elicit an antiidiotypic response (Ab2), which can be of three types: (1) Ab2β, which is directed to the paratope of Ab1, and presents the internal image of antigen epitope x; (2) Ab2γ, which is directed to the paratope of Ab1 but does not carry the internal image; (3) Ab2α, which is directed to nonparatopic or framework idiotopes of Ab1.

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Gavalchin, Jerrie(Nov 2011) Idiotypes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000912.pub2]