Human anti‐IgE antibodies by repertoire cloning

Vogel, Monique; Miescher, Sylvia; Biaggi, Christine; Stadler, Beda M.

doi:10.1002/eji.1830240529

Cited by 52 publications

(58 citation statements)

References 26 publications

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“…This model (shown in Fig. 9) is supported by the observation that IgE binds to FCgRIa and nonanaphylactogenic antibodies in 1 :1 stoichiometry (25,26,64,65). In contrast, one IgE molecule binds two anaphylactic antibodies (26).…”

Section: Mapping Of the Complementary Binding Site Between Hnman Ige mentioning

confidence: 60%

“…These findings are summarized in Figs. lOA and B. Interestingly, several monoclonal and naturally occurring anti-hlgE antibodies have been described which block the binding of IgE to Fc^^RI, but fail to cross-link receptor-bound IgE and initiate degranulation (25,26,64). As reviewed earlier in this series, some of these anti-hlgE antibodies have shown promise in clinical trials after humanization, where they were used for the passive immunization of asthmatic patients.…”

Section: Mapping Of the Complementary Binding Site Between Hnman Ige mentioning

confidence: 99%

“…It sensitizes, but does not activate, target-cell degranulation until the ligand is aggregated, usually by antigen, less frequently by anti-IgE antibodies and lectins (25)(26)(27)(28) …”

mentioning

confidence: 99%

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Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

Helm

Spivey

Padlan

1997

Allergy

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Section: Mapping Of the Complementary Binding Site Between Hnman Ige mentioning

confidence: 60%

Section: Mapping Of the Complementary Binding Site Between Hnman Ige mentioning

confidence: 99%

See 1 more Smart Citation

Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

Helm

Spivey

Padlan

1997

Allergy

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“…Infected bacteria were cloned on selective media as previously described (29), and phagemid DNA was purified (Wizard Plus SV Minipreps; Promega). Clones were sequenced at Microsynth.…”

Section: Sequencingmentioning

confidence: 99%

A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the FcεRIα

Bobrzynski

Fux

Vogel

et al. 2005

The Journal of Immunology

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Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the α domain of the high-affinity IgE receptor (FcεRIα) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcεRIα Abs are present in the germline repertoire, we constructed a phage Fab display library from human cord blood, which represents the naive immune repertoire before exposure to exogenous Ags. All isolated clones specific to the FcεRIα had the same sequence. This single IgM Ab, named CBMα8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcεRIα recognized by both CBMα8 and the previously isolated anti-FcεRIα Abs from autoimmune and healthy donors. This common epitope on FcεRIα coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMα8-like specificity, but with a significantly lower affinity in i.v. Ig, a therapeutic multidonor IgG preparation. We propose a hypothesis of escape mutants, whereby the resulting lower affinity IgG anti-FcεRIα Abs are rendered less likely to compete with IgE for binding to FcεRIα.

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“…Production of rabbit anti-phage Ab (RaP) 6 was described earlier (18). Abs Le27 and BSW17 are described elsewhere (11).…”

Section: Antibodiesmentioning

confidence: 99%

Molecular Basis for Nonanaphylactogenicity of a Monoclonal Anti-IgE Antibody

Rudolf

Zuercher

Nechansky

et al. 2000

The Journal of Immunology

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IgE Abs mediate allergic responses by binding to specific high affinity receptors (FcεRI) on mast cells and basophils. Therefore, the IgE/FcεRI interaction is a target for clinical intervention in allergic disease. An anti-IgE mAb, termed BSW17, is nonanaphylactogenic, although recognizing IgE bound to FcεRI, and interferes with binding of IgE to FcεRI. Thus, BSW17 represents a candidate Ab for treatment of IgE-mediated disorders. By panning BSW17 against random peptide libraries displayed on phages, we defined mimotopes that mimic the conformational epitope recognized on human IgE. Two types of mimotopes, one within the Cε3 and one within the Cε4 domain, were identified, indicating that this mAb may recognize either a large conformational epitope or eventually two distinct epitopes on IgE. On the basis of alignments of the two mimotopes with the human IgE sequence, we postulate that binding of BSW17 to the Cε3 region predominantly blocks binding of IgE to FcεRI, leading to neutralization of IgE. Moreover, binding of BSW17 to the Cε4 region may explain how BSW17 recognizes FcεRI-bound IgE, and binding to this region may also interfere with degranulation of IgE sensitized cells (basophils and mast cells). As a practical application of these findings, mimotope peptides coupled to a carrier protein may be used for the development of a peptide-based anti–allergy vaccine by induction of anti-IgE Abs similar to the current approach of using humanized nonanaphylactogenic anti-IgE Abs as a passive vaccine.

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Human anti‐IgE antibodies by repertoire cloning

Cited by 52 publications

References 26 publications

Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the FcεRIα

Molecular Basis for Nonanaphylactogenicity of a Monoclonal Anti-IgE Antibody

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