An antiidiotypic antibody that recognizes the beta-adrenergic receptor.

Homcy, Charles J.; Rockson, Stanley G.; Haber, Edgar

doi:10.1172/jci110550

Cited by 100 publications

(22 citation statements)

References 19 publications

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“…Moreover, evidence was provided that excretion of intestinal leukotriene metabolites with stool competes with their enterohepatic circulation (17). Since the observation by Sege and Peterson that anti-Id against antiinsulin induces a physiological response (3), several reports have demonstrated antagonistic effects of anti-Id rds well (18,19). Of particular importance, therefore, was the finding that anti-Id indeed, but not preimmune IgG, was highly efficient in inhibiting immediate-type skin reactions.…”

Section: Discussionmentioning

confidence: 99%

Protection against the staphylococcal enterotoxin-induced intestinal disorder in the monkey by anti-idiotypic antibodies.

Reck¹,

Scheuber²,

Londong³

et al. 1988

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

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The staphylococcal enterotoxin serotype B (SEB)-induced enteric intoxication and the immediate-type reaction in the skin of unsensitized monkeys was used to define whether agents competing with SEB for target cell receptors may inhibit pathophysiological effects. For this purpose a duodenal provocation test was developed by use of a pediatric gastroscope, allowing the evaluation of the influence of antagonists on the intestinal disorder upon SEB challenge at the same duodenal site. First, carboxymethylation of histidine residues of SEB caused a complete loss of emetic and skinsensitizing activity without changing the immunological specificity. However, carboxymethylated SEB is a strong inhibitor of enteric intoxications and immediate-type skin reactions upon SEB challenge. Second, after immunization of BALB/c mice with monoclonal anti-SEB antibodies, monoclonal antiidiotypic antibodies (anti-Id) were obtained by the "hybridoma technique" and purification by idiotype-affinity chromatography. Anti-Id specifically inhibited the binding of horseradish peroxidase-labeled anti-SEB to the ligand, and SEB blocked as well the interaction of these two antibody species, indicating a high degree of binding-site selectivity. Anti-Id completely protected against emetic response and diarrhea upon duodenal provocation with SEB and inhibited immediate-type skin reactions as well. Further, anti-Id acted as an antagonist without triggering biologic functions themselves. This shows that anti-Id constitute a useful tool to protect against a bacterial toxininduced intestinal disorder.Staphylococcal enterotoxins (SE) are responsible for one of the most common types of food poisoning in humans (1). All SE produce emesis and diarrhea in humans and other primates as a result of oral administration, whereas the toxin appears to have little, if any, clinical effect in other laboratory animals (1). Although considerable efforts have been expended on attempts to define the pathogenesis, so far very little information has been available on the mode and cellular site of SE action in the gastrointestinal tract.Recently, however, evidence was provided that unsensitized monkeys develop an immediate-type reaction in the skin upon intradermal challenge with SE serotype B (SEB; ref.2). As shown by a series of experiments, SEB administered intradermally causes skin reactions by affecting mast cells (2). This type of nonimmunological mast cell stimulation by SEB offered a new approach, providing a model for investigating the mechanisms of SEB action. In addition, evidence was provided that carboxymethylation of SEB resulted in a loss of toxicity associated with the complete abrogation of skin-sensitizing activity without changing the immunological specificity of the toxin. It has been established that carboxymethylated SEB (CM-SEB) could compete with SEB for binding sites on the target-cell surface (2). To define whether SEB exerts its effect on mast cells by binding to specific celt-surface receptors or whether a less specific type of ligand-...

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Section: Discussionmentioning

confidence: 99%

Protection against the staphylococcal enterotoxin-induced intestinal disorder in the monkey by anti-idiotypic antibodies.

Reck¹,

Scheuber²,

Londong³

et al. 1988

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

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“…It has to be delineated, however, whether SEB exerts its effect on mast cells by binding to specific cell-surface receptors or whether some less-specific type of ligand-cell membrane interaction is involved. It has been shown that anti-Id raised against antibodies to ligands that interact with cellular receptors also react with the corresponding cell-surface receptors (4,5,14). Therefore, the anti-Id reagent may also be a useful tool to study the nature of SEB binding to the mast cell membrane.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown previously, that anti-idiotypic antibodies (anti-Id) raised against the binding sites of anti-hormone antibodies are able to interact with the hormone receptors (4,5). Such an approach might be successfully applied with SEB, a more complex ligand than hormones, to identify whether ligand-specific receptors actually exist on the target cell membrane.…”

mentioning

confidence: 99%

Anti-idiotypic antibodies that inhibit immediate-type skin reactions in unsensitized monkeys on challenge with staphylococcal enterotoxin.

Bamberger¹,

Scheuber²,

Sailer-Kramer³

et al. 1986

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

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The staphylococcal enterotoxin B (SEB)-induced immediate-type skin reaction in unsensitized monkeys was used as a nonimmunological mast cell stimulus to examine whether the toxin exerts its effect via specific receptors on the target cell membrane. Anti-idiotypic antibodies (anti-Id) were raised in BALB/c mice against monoclonal anti-SEB antibodies (anti-SEB) and purified by idiotype affinity chromatography. The anti-Id nature of the antibody was demonstrated by its ability to inhibit the binding of 125I-labeled anti-SEB to the ligand in a concentration-dependent manner. Moreover, binding of anti-SEB to anti-Id was antagonized by the SEB ligand in a competitive way. These antibodies completely abolished skin reactions in unsensitized monkeys on challenge with SEB and impeded those provoked by staphylococcal enterotoxins A and C1 but did not have the biological activity of the toxin. These data are compatible with the view that receptors for staphylococcal enterotoxins may exist on the membrane of mast cells in the skin of unsensitized monkeys. The data suggest an experimental approach for producing anti-cell receptor antibodies that are of potential value to influence the course of staphylococcal enterotoxin-mediated effects.Staphylococcal enterotoxin has been implicated in one of the most prevalent types of food-borne debilitating enteric intoxication in humans. Next to man, monkeys are found to be the most susceptible to oral administration ofthe enterotoxin, which produces emesis and diarrhea, the classic symptoms of such food poisoning, whereas the toxin appears to have little clinical effect in other laboratory animals (1).Although considerable effort has been expended on attempts to clarify the pathogenesis, very little, if any, information was available on the mode and cellular site of staphylococcal enterotoxin action in the gastrointestinal tract (2).Recently, however, detailed evidence was provided that staphylococcal enterotoxin B (SEB) causes, in addition to emesis, immediate-type skin reactions in unsensitized monkeys by affecting cutaneous mast cells. That mast cell mediators are involved is reflected by the fact that both the skin reactions and the emetic responses to SEB are completely abolished by histamine H2 receptor antagonists and calcium channel blockers (3). Another feature of this study was the loss of toxicity associated with the complete abrogation of skin-sensitizing activity without changing the immunological specificity of SEB after carboxymethylation of the toxin. Furthermore it has been established that carboxymethylated SEB can in fact specifically inhibit the response to native SEB in unsensitized skin sites. Thus, it is reasonable to assume that carboxymethylated SEB competitively antagonizes the action of native SEB on binding sites of mast cells but is incapable of promoting activation signals by itself. It has to be delineated, however, whether SEB exerts its effect on mast cells by binding to specific cellsurface receptors or whether some less-specific type of ligand...

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“…Such antiidiotypic antibodies that recognize and inhibit ligand binding to the /3-adrenergic receptor, as well as inhibiting receptor-mediated cyclase activation, have already been developed by use of /9-antagonist-specific antibodies as immunogens. 11 It is probable, therefore, that these a-antagonist-specific antibodies, which have ligand recognition properties similar to a-adrenergic receptors, will yield antiidiotypic antibodies with high affinity for the biological receptor. Indeed, antisera with marked antiidiotypic activity have already been raised (table 2), although cross reactivity with the a-adrenergic receptor itself has not yet been observed.…”

Section: -187mentioning

confidence: 99%

Antibodies to the alpha 1- and alpha 2-selective antagonists prazosin and yohimbine as probes of the alpha-adrenergic binding sites.

Graham¹,

Hess²,

Haber³

et al. 1982

Hypertension

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SUMMARY Antibodies were raised against a newly synthesized analog (CP57.609) of the o,-selective antagonist prazosin, and against the a.-selective antagonist, yohimbine, by Immunization of rabbits with antigens prepared by covalent linkage of these Uganda to albumin. Competitive Inhibition of [ a H]prazosln binding to anti-CP57,609 antiserum by a variety of nnlabeled Uganda revealed a spectrum of antibody specificity, with a r selective agents competing more potently than a,-seiectiTe llgands. In contrast, a,-selective ligands competed more potently with the binding of ['H]yofaimbine to the anti-yohlmbine antiserum than a^-selective agents. These respective antisera were subjected to affinity fractionation on a CP57,609-or yohimbine-Sepharose 4B resin. Fractions from the CP57,609 resin were eluted successively with phentolamine (10~'M), prazosin (10 4 M), and guanidine (5M), and from the yohimbine resin with prazosin (10^M), yohimbine (HMM), and guanldlne (SM). The binding profiles of these fractions differed, and in certain fractions the relative order of potency of adrenergic agents was almost identical to that observed with membrane a-adrenergic receptors. Moreover, using these eluted fractions as immunogens, antisera have been obtained which, in the initial bleeds, already possess antiidiotypic activity. These findings therefore suggest that affinity fractionation of antibodies raised against a r and a t -selective antagonists may provide useful analogs for the further study of the ligand recognition properties of a-adrenergic receptors. Additionally, it is probable that antiidiotypic antisera will be developed which will recognize the a-adrenergic binding sites. A S with the /?-adrenergic system, the binding of pharmacologically active agents to a membrane receptor is the requisite first step in aadrenergic modulation of cellular processes. On the basis of pharmacologic and radioligand binding studies, these receptors have been identified in a number of tissues 1 and subclassified according to their relative affinities for a variety of a-adrenergic agonists and antagonists into a x -and at-subtypes. J However, little is known about the molecular interaction of aadrenergic agents with these membrane-binding sites, as the purification of the receptor proteins and their structural characterization have not been performed. As an alternative indirect approach to studies of the /8-adrenergic receptor, we have developed /8-antagonistspecific antiserum and demonstrated that its component antibodies can be used as probes to study the ligand recognition properties of the /J-adrenergic receptor. 8 In the present paper, a similar approach has been applied to studies of the recognition properties of a-adrenergic receptors by the development and affinity fractionation of a,-and a a -selective antagonist-specific antibodies.

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An antiidiotypic antibody that recognizes the beta-adrenergic receptor.

Abstract: A B S T R A C T Antialprenolol rabbit antibodies were fractionated on an acebutolol affinity resin, followed by L-propranolol elution so

Cited by 100 publications

References 19 publications

Protection against the staphylococcal enterotoxin-induced intestinal disorder in the monkey by anti-idiotypic antibodies.

Protection against the staphylococcal enterotoxin-induced intestinal disorder in the monkey by anti-idiotypic antibodies.

Anti-idiotypic antibodies that inhibit immediate-type skin reactions in unsensitized monkeys on challenge with staphylococcal enterotoxin.

Antibodies to the alpha 1- and alpha 2-selective antagonists prazosin and yohimbine as probes of the alpha-adrenergic binding sites.

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