Idiotypic Games within the Immune Network

Slaoui, Moncef; Urbain-Vansanten, G; Demeur, Cécile; Léo, Oberdan; Marvel, Jacqueline; Moser, Muriel; Tassignon, Jean-Pierre; Greene, Mark I.; Urbain, Jacques

doi:10.1111/j.1600-065x.1986.tb01478.x

Cited by 14 publications

(4 citation statements)

References 46 publications

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“…2). Several reports show that the injection of a given antibody results in increased synthesis of antibodies with similar specificity and/or idiotypes (31,(33)(34)(35)(36). These data have been taken in support of, or interpreted in the frame of, Jerne's network theory (23) (that is, in the usual terminology, reflecting Ab2-instructed antibody synthesis).…”

Section: Working Principlesmentioning

confidence: 79%

Working principles in the immune system implied by the "peptidic self" model.

Kourilsky¹,

Chaouat²,

Rabourdin–Combe³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The hypothesis that self as well as foreign proteins are processed into peptides and presented by major histocompatibility complex antigens leads to a set of working principles that could govern cellular interactions in immune responses. In particular, "idiopeptides," derived from immunoglobulins and T-cell receptors and recognized by appropriate T cells, are expected to play an important regulatory role. We show here that these speculations fit into a consistent view of the immune system.In the past few years, a remarkable series of experiments has cast light on the function of class I and class II molecules of the major histocompatibility complex (MHC). A growing body of evidence enforces the view that class II MHC molecules bind peptides derived from "processed" (i.e., partially degraded) antigen and expose them on the cell surface (1-3). Importantly, recent experiments indicate that class I MHC molecules could do the same (4-6). The primary function of MHC molecules might thus be to present peptides derived from processed proteins.Assigning a molecular function to MHC molecules is a major accomplishment because they play a pivotal role in regulatory interactions between cells of the immune system. It is well established that the activation and action of various types of T lymphocytes (TH, helper; Ts, suppressor; CTL, cytolytic) requires recognition by T-cell receptors (TCR) of (processed) antigen in association with MHC molecules on the surface of antigen-presenting cells (APCs) or target cells.Under the assumption that the actual function of MHC molecules relies on peptide presentation, we have proposed a logical generalization based on an interpretation of results by Townsend et al. (4, 5)-namely, that self, as well as foreign proteins, can yield peptides presented by MHC molecules (7,8). Cells expressing MHC molecules would thus be permanently coated with a set of distinct peptides somehow reflecting their protein content. For example, somatic cells, most of which express class I MHC molecules, would display myriads of self peptides associated to the latter. APCs (i.e., macrophages, dendritic cells, B cells), which express both class I and class II MHC molecules, would be loaded with antigen-derived peptides in addition to self peptides. Finally, B cells producing a given antibody would expose peptides derived from it, called antibody idiopeptides (designated Ab), while T cells expressing TCR could expose TCR idiopeptides (designated TCR). Therefore, the generalization proposed under our initial peptidic self model (7, 8) leads to two major predictions: (i) the presentation of self peptides by MHC molecules, and (it) the existence of idiopeptides, which, as discussed below, could constitute an important class of regulatory elements. Here, we delineate the implications arising from these premises and show that they lead to a consistent view of the immune system. WORKING PRINCIPLESPresentation by MHC Molecules. So far, little is known about the mechanisms of antigen presentation, but they are likely...

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Section: Working Principlesmentioning

confidence: 79%

Working principles in the immune system implied by the "peptidic self" model.

Kourilsky¹,

Chaouat²,

Rabourdin–Combe³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, I have overlooked the fact that Ab2 antibodies may be functionally classified into four major categories (26,(31)(32)(33).…”

Section: The Modelmentioning

confidence: 99%

A simple model for the immune network.

Parisi

1990

Proc. Natl. Acad. Sci. U.S.A.

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In this note I present a simple model for the idiotypic network among antibodies and study its relevance for the maintenance of immunological memory; in particular, the memory capacity of such a model is studied. Some of the similarities with the spin glass model and with neural networks are discussed.Comparison of the brain and the immune system has been quite fruitful in the past (1, 2). Stimulated by the analogy with the brain and by the discovery of the idiotypy (3), Jerne has proposed a network theory for the immune system. Roughly speaking, the production of a given antibody elicits (or suppresses) the production of other antibodies that elicit (or suppress) the production of other antibodies and so on. This is reminiscent of the way in which a firing neuron may induce (or inhibit) the firing of other neurons.In this note I study a specific model that demonstrates that a functional network of antibodies may be possible. I concentrate on modeling the behavior of the immune system in absence of any driving force of external antigens in order to study the maintenance of the immunologic memory. The aim is not to produce a detailed model of the system, which could be used for quantitative comparison with the experimental data, but rather to provide a simple theoretical framework in which different questions may be discussed. For this reason the construction of the model is simplified as much as possible, in the same spirit as the construction of formal neurons (4) and of a symmetric neural network (5). If the model is sufficiently simple, as the one presented here, some results may be derived analytically, without recourse to simulations, and many results obtained in statistical mechanics become available. The use of statistical techniques is inescapable, if we want to understand the behavior of a system in which >106 different kinds of molecules interact.It is well established that antiidiotypic antibodies (i.e., antibodies against antibodies) are normally generated in the process of the response to an external antigen [especially by repeated vaccination (6)]. Such antiidiotypic antibodies also exist in unprimed animals (7). Although one of the main assumptions of the network theory is satisfied, the functional role of the network is not fully understood and a spectrum of different conclusions can be found in the literature. Moreover, if we accept that the network is not a pure accident (8) and that it has a precise functional role, its properties are not clear. There are some crucial points on which there is no general agreement and various options are available.(i) It is not established whether the autoantibodies, which arise in response to a given antibody and have a functional role, are produced by a small set of high responder clones or by a large set of low responder clones.(ii) A related question concerns the effect of a new antigen on the behavior of the network: Does it modify the whole network of antibodies or does the perturbation remain localized within a given set? Does the network remain ...

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“…Taking advantage of the expertise developed by his mentor and predecessor, Raymond Jeener (1904–1995) in the field of virology [4], he undertook a detailed analysis of the serological immune response of animals inoculated with the Tobacco Mosaic Virus, paving the way for the study of immune repertoires, tolerance and the manipulation of immune responses using antibodies to antibodies, i.e. anti‐idiotypic antibodies [5]. He was one the main supporters of the idiotypic network theory developed by Niels Jerne (1911–1994).…”

Section: From 1978 To 1989mentioning

confidence: 99%