Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

Helm, Birgit A.; Spivey, Alan C.; Padlan, Eduardo A.

doi:10.1111/j.1398-9995.1997.tb02518.x

Cited by 35 publications

(37 citation statements)

References 94 publications

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“…We have also produced a number of other soluble Fc receptors in P. pastoris, including Fc␥RIIa (M. Powell and P. M. Hogarth, unpublished observations) and Fc␣R (46). Others have reported expression of sFc⑀RI␣ in P. pastoris, although no further details were given (18,47).…”

Section: Discussionmentioning

confidence: 99%

Mutagenesis Within Human FcεRIα Differentially Affects Human and Murine IgE Binding

Mackay

Hulett

Cook

et al. 2002

The Journal of Immunology

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Soluble fragments of the α-chain of FcεRI, the high-affinity receptor for IgE, compete with membrane-bound receptors for IgE and may thus provide a means to combat allergic responses. Mutagenesis within FcεRIα is used in this study, in conjunction with the crystal structure of the FcεRIα/IgE complex, to define the relative importance of specific residues within human FcεRIα for IgE binding. We have also compared the effects of these mutants on binding to both human and mouse IgE, with a view to evaluating the mouse as an appropriate model for the analysis of future agents designed to mimic the human FcεRIα and attenuate allergic disease. Three residues within the C-C′ region of the FcεRI α2 domain and two residues within the α2 proximal loops of the α1 domain were selected for mutagenesis and tested in binding assays with human and mouse IgE. All three α2 mutations (K117D, W130A, and Y131A) reduced the affinity of human IgE binding to different extents, but K117D had a far more pronounced effect on mouse IgE binding, and although Y131A had little effect, W130A modestly enhanced binding to mouse IgE. The mutations in α1 (R15A and F17A) diminished binding to both human and mouse IgE, with these effects most likely caused by disruption of the α1/α2 interface. Our results demonstrate that the effects of mutations in human FcεRIα on mouse IgE binding, and hence the inhibitory properties of human receptor-based peptides assayed in rodent models of allergy, may not necessarily reflect their activity in a human IgE-based system.

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Section: Discussionmentioning

confidence: 99%

Mutagenesis Within Human FcεRIα Differentially Affects Human and Murine IgE Binding

Mackay

Hulett

Cook

et al. 2002

The Journal of Immunology

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“…Methods to competitively inhibit the binding of IgE to mast cells have been explored. It was reported that Fce fragments derived from human myeloma IgE by cleavage with papain can competitively inhibit passive cutaneous anaphylaxis [118]. This has led to the development of smaller Fce-derived peptides as potential therapeutic blocking agents.…”

Section: Humanized Monoclonal Antibodiesmentioning

confidence: 99%

Current immunological approaches for management of allergic rhinitis and bronchial asthma

2009

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A large population world over is affected with allergic diseases and asthma. Pharmacotherapy for allergic diseases and asthma is effective in controlling symptoms but on discontinuation of medication, symptoms reoccur. In contrast, immunotherapy modifies and corrects the underlying pathological immune responses in an antigen-specific manner. Immunotherapy shows an increase in IgG (blocking antibody) that competes with IgE for allergen, inhibiting the release of inflammatory mediators. Recent studies suggest that immunotherapy acts by modifying CD4+ T-cell responses either by immune deviation, T-cell anergy and/or both. Current immunological approaches for management of allergies and asthma involve immunization with native allergen, modified allergen, peptides/cDNA of allergen, anti-IgE, adjuvants coupled allergen, including immunostimulatory DNA sequences, cytokines, and bacterial products. These approaches modulate the immune response and are intended to give long-term benefit.

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“…These cells bear receptors (FceRI) for immunoglobulins (Ig) of the IgE isotype, and cross-linking of FceRI by allergens induces the rapid release of newly synthesised and preformed mediators, including histamine, proteoglycans and endoproteases, which are stored in cytoplasmic granules (for review see [1]). Receptor-mediated exocytosis requires fusion of the secretory granule membrane with the plasma-membrane in response to an IgE-mediated, antigen-induced stimulus.…”

Section: Introductionmentioning

confidence: 99%

“…Receptor-mediated exocytosis requires fusion of the secretory granule membrane with the plasma-membrane in response to an IgE-mediated, antigen-induced stimulus. Numerous studies have demonstrated a causal relationship between the secretion of granule contents and immediate type I hypersensitivity responses [1]. However, basophils from at least 20% of the human population do not respond to an IgE-receptormediated stimulus with degranulation and release of the mediators of the allergic response [2].…”

Section: Introductionmentioning

confidence: 99%

Two-dimensional electrophoresis reveals differential protein expression in high- and low-secreting variants of the rat basophilic leukaemia cell line

et al. 2000

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The aim of this investigation was the identification of cellular proteins that confer a high secretory phenotype on subclones of the rat basophilic leukaemia (RBL) cell line as a model of mast cell regulated degranulation. Following protein separation by two-dimensional (2-D) electrophoresis and silver staining, more than 2000 polypeptide "spots" were resolved reproducibly. Higher sample loads and Coomassie blue staining facilitated the identification by delayed extraction-matrix-assisted laser desorption/ionization (DE-MALDI) mass spectrometry of several polypeptides that were differentially expressed in the high- and low-secreting clones. Several proteins were identified whose expression could contribute to the difference in secretory phenotype. Furthermore, silver-stained 2-D gel patterns suggested differential expression of proteins in the 20-25 kDa and the pI 4.5-7.5 range, characteristic of small guanosine 5'-triphosphate (GTP)-binding proteins. By a combination of "GTP overlay" and immunoblotting, we were able to demonstrate differential expression of small GTP binding-proteins, including Rab3 proteins, in high-and low-secreting clones. The sensitivity of this complementary approach facilitated the detection of some GTP binding and Rab3 proteins, whose expression was not evident in silver-stained 2-D gels.

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Peptide blocking of IgE/receptor interaction: possibilities and pitfalls

Cited by 35 publications

References 94 publications

Mutagenesis Within Human FcεRIα Differentially Affects Human and Murine IgE Binding

Mutagenesis Within Human FcεRIα Differentially Affects Human and Murine IgE Binding

Current immunological approaches for management of allergic rhinitis and bronchial asthma

Two-dimensional electrophoresis reveals differential protein expression in high- and low-secreting variants of the rat basophilic leukaemia cell line

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