Structural mapping of membrane-bound immunoglobulin E-receptor complexes: use of monoclonal anti-IgE antibodies to probe the conformation of receptor-bound IgE

Biochemistry ◽  
1985 ◽  
Vol 24 (22) ◽  
pp. 6260-6267 ◽  
Author(s):  
David Holowka ◽  
Daniel H. Conrad ◽  
Barbara Baird
Keyword(s):  
Immunoglobulin E ◽  
Structural Mapping ◽  
Ige Antibodies ◽  
Receptor Complexes ◽  
Membrane Bound

scholarly journals Bispecific T-Cell Engagers Targeting Membrane-Bound IgE

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1568
Author(s):  
Aleksandra Rodak ◽  
Gerhard Stadlmayr ◽  
Katharina Stadlbauer ◽  
Dominic Lichtscheidl ◽  
Madhusudhan Reddy Bobbili ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Jurkat Cells ◽  
Single Chain ◽  
Ige Antibodies ◽  
Serum Ige ◽  
Single Chain Fv ◽  
Membrane Bound

The increased incidence of allergies and asthma has sparked interest in IgE, the central player in the allergic response. Interaction with its high-affinity receptor FcεRI leads to sensitization and allergen presentation, extracellular membrane-proximal domain in membrane IgE can act as an antigen receptor on B cells, and the interaction with low-affinity IgE receptor CD23 additionally influences its homeostatic range. Therapeutic anti-IgE antibodies act by the inhibition of IgE functions by interfering with its receptor binding or by the obliteration of IgE-B cells, causing a reduction of serum IgE levels. Fusion proteins of antibody fragments that can act as bispecific T-cell engagers have proven very potent in eliciting cytotoxic T-lymphocyte-mediated killing. We have tested five anti-IgE Fc antibodies, recognizing different epitopes on the membrane-expressed IgE, for the ability to elicit specific T-cell activation when expressed as single-chain Fv fragments fused with anti-CD3ε single-chain antibody. All candidates could specifically stain the cell line, expressing the membrane-bound IgE-Fc and bind to CD3-positive Jurkat cells, and the specific activation of engineered CD3-overexpressing Jurkat cells and non-stimulated CD8-positive cells was demonstrated for 8D6- and ligelizumab-based bispecific antibodies. Thus, such anti-IgE antibodies have the potential to be developed into agents that reduce the serum IgE concentration by lowering the numbers of IgE-secreting cells.

ASTHMA AND IMMUNOGLOBULIN E (IgE) ANTIBODIES AFTER RESPIRATORY SYNCYTIAL VIRUS (RSV) BRONCHIOLITIS: A PROSPECTIVE COHORT STUDY WITH MATCHED CONTROLS

PEDIATRICS ◽  
1996 ◽  
Vol 98 (2) ◽  
pp. 329-329
Author(s):  
James E. Gern
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Respiratory Syncytial Virus ◽  
Family History ◽  
Prospective Cohort ◽  
Immunoglobulin E ◽  
Specific Ige ◽  
Ige Antibodies ◽  
History Of ◽  
Syncytial Virus

RSV bronchiolitis was the most important risk factor for the development of asthma and allergen-specific IgE, although a family history of atopy or asthma further increased the risk.

scholarly journals Large-scale co-aggregation of fluorescent lipid probes with cell surface proteins.

1994 ◽  
Vol 125 (4) ◽  
pp. 795-802 ◽  
Author(s):  
J L Thomas ◽  
D Holowka ◽  
B Baird ◽  
W W Webb
Keyword(s):  
Cell Surface ◽  
Large Scale ◽  
Plasma Membranes ◽  
Immunoglobulin E ◽  
Large Fraction ◽  
Surface Antigens ◽  
Specific Cell ◽  
Cell Surface Antigens ◽  
Receptor Complexes ◽  
Ige Receptors

Large scale aggregation of fluorescein-labeled immunoglobulin E (IgE) receptor complexes on the surface of RBL cells results in the co-aggregation of a large fraction of the lipophilic fluorescent probe 3,3'-dihexadecylindocarbocyanine (diI) that labels the plasma membranes much more uniformly in the absence of receptor aggregation. Most of the diI molecules that are localized in patches of aggregated receptors have lost their lateral mobility as determined by fluorescence photobleaching recovery. The diI outside of patches is mobile, and its mobility is similar to that in control cells without receptor aggregates. It is unlikely that the co-aggregation of diI with IgE receptors is due to specific interactions between these components, as two other lipophilic probes of different structures are also observed to redistribute with aggregated IgE receptors, and aggregation of two other cell surface antigens also results in the coredistribution of diI at the RBL cell surface. Quantitative analysis of CCD images of labeled cells reveals some differences in the spatial distributions of co-aggregated diI and IgE receptors. The results indicate that cross-linking of specific cell surface antigens causes a substantial change in the organization of the plasma membrane by redistributing pre-existing membrane domains or causing their formation.

Use of Radioimmunoassay to Determine the Nature, Quantity and Source of Allergenic Contamination of Sunflower Butter

1983 ◽  
Vol 46 (7) ◽  
pp. 625-628 ◽  
Author(s):  
JOHN W. YUNGINGER ◽  
MARY B. GAUERKE ◽  
RICHARD T. JONES ◽  
MARY JO E. DAHLBERG ◽  
STEVEN J. ACKERMAN
Keyword(s):  
Allergic Reaction ◽  
Food Processing ◽  
Immunoglobulin E ◽  
Solid Phase ◽  
Peanut Butter ◽  
Manufacturing Plant ◽  
Ige Antibodies ◽  
Naturally Occurring ◽  
Solid Phase Radioimmunoassay ◽  
Butter Production

A girl known to be allergic to peanuts experienced a mild allergic reaction after eating sunflower butter, a peanut butter facsimile prepared from sunflower nuts. After learning that the same manufacturing plant also produced peanut butter, we examined several sunflower butter preparations for peanut butter contamination by a solid-phase radioimmunoassay which used naturally-occurring immunoglobulin E (IgE) antibodies from known peanut-sensitive individuals. Peanut butter contamination, ranging from 0.3 to 3.3%, was found in six of eight sunflower butter samples, including both creamy and chunky varieties, and including lots prepared with either peanut oil or palm oil. We concluded that inadequate cleaning of food processing machines following peanut butter production permitted the contamination by peanut butter of subsequent jars of sunflower butter in amounts which could pose risks to peanut-sensitive individuals.

Staphylococcal Exotoxins and Nasal Polyposis: Analysis of Systemic and Local Responses

2005 ◽  
Vol 19 (4) ◽  
pp. 327-333 ◽  
Author(s):  
Anju Tripathi ◽  
Robert Kern ◽  
David B. Conley ◽  
Kristin Seiberling ◽  
Julie C. Klemens ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nasal Polyposis ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Cell Receptor ◽  
Specific Ige ◽  
Sinus Surgery ◽  
Ige Antibodies

Background Staphylococcal exotoxins have been implicated in the pathogenesis of several chronic inflammatory diseases including atopic dermatitis (AD), asthma, and, most recently, chronic rhinosinusitis with nasal polyposis (CRS/NP). In severe AD, these toxins act both as superantigens (SAg), triggering massive T-cell activation, and as conventional allergens, triggering toxin-specific immunoglobulin E (IgE) in the serum. In CRS/NP, evidence for both processes has been reported but it is unclear whether these processes are linked. The aim of this study was to correlate SAg activity as inferred by staphylococcal-specific T-cell receptor (TCR) V-β expansion in the polyp and blood of CRS/NP patients with staphylococcal-specific anti-IgE antibodies in the serum. Methods IgE antibodies to staphylococcal exotoxin A (SEA), staphylococcal exotoxin B (SEB), and toxic shock syndrome toxin (TSST) 1 were measured in the serum of 12 individuals with CRS/NP before functional endoscopic sinus surgery. Flow cytometry was used to analyze the SEA, SEB, and TSST-1–specific TCR V-β domains on the T cells from the polyp and blood of these patients. Results Serum SEA-, SEB-, and TSST-1-specific IgE antibodies were detected in 0/12 (0%), 6/12 (50.0%), and 9/12 (75%) of CRS/NP patients, respectively. Evidence of SAg effect in the polyp lymphocytes (TCR V-β expansion in both CD4+ and CD8+ subsets) was noted in 7/12 (58.3%) patients. Five of 6 CRS/NP patients had overlapping evidence of a systemic IgE response and TCR V-β expansion, suggestive of exposure to the same exotoxin. No patients had evidence a SAg effect in blood lymphocytes. Nine of 12 subjects also had coexistent asthma. Conclusion These results provide evidence for a local SAg effect in 7/12 (58.3%) polyp patients and establish a positive correlation of V-β expansion with the presence of corresponding toxin-specific IgE in the serum.

scholarly journals IgE Antibodies against Cancer: Efficacy and Safety

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 55
Author(s):  
Jitesh Chauhan ◽  
Alex J. McCraw ◽  
Mano Nakamura ◽  
Gabriel Osborn ◽  
Heng Sheng Sow ◽  
...  
Keyword(s):  
Perceived Risk ◽  
Immunoglobulin E ◽  
Ex Vivo ◽  
Risk Mitigation ◽  
Antitumour Activity ◽  
Allergic Diseases ◽  
Type I ◽  
Ige Antibodies

Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumours. This has led to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here, we bring together the properties of IgE antibodies pivotal to the hypothesis for superior antitumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anticancer IgE therapeutic.

scholarly journals Hydrogen Exchange Mass Spectrometry of Functional Membrane-Bound Chemotaxis Receptor Complexes

Biochemistry ◽  
2013 ◽  
Vol 52 (49) ◽  
pp. 8833-8842 ◽  
Author(s):  
Seena S. Koshy ◽  
Stephen J. Eyles ◽  
Robert M. Weis ◽  
Lynmarie K. Thompson
Keyword(s):  
Mass Spectrometry ◽  
Hydrogen Exchange ◽  
Exchange Mass Spectrometry ◽  
Receptor Complexes ◽  
Hydrogen Exchange Mass Spectrometry ◽  
Functional Membrane ◽  
Membrane Bound

scholarly journals High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes

Science ◽  
2018 ◽  
Vol 362 (6420) ◽  
pp. 1306-1309 ◽  
Author(s):  
Derek Croote ◽  
Spyros Darmanis ◽  
Kari C. Nadeau ◽  
Stephen R. Quake
Keyword(s):  
B Cell ◽  
Immunoglobulin E ◽  
Variable Region ◽  
Cross Reactivity ◽  
Food Allergies ◽  
Ige Antibodies ◽  
High Affinity ◽  
Helminth Infections ◽  
Life Threatening ◽  
Antibody Class

Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

scholarly journals IgE Antibodies: From Structure to Function and Clinical Translation

Antibodies ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 19 ◽  
Author(s):  
Brian Sutton ◽  
Anna Davies ◽  
Heather Bax ◽  
Sophia Karagiannis
Keyword(s):  
Conformational Changes ◽  
Immunoglobulin E ◽  
Fc Receptors ◽  
Solid Tumours ◽  
Clinical Translation ◽  
Therapeutic Modality ◽  
Ige Antibodies ◽  
Effector Functions ◽  
Anti Cancer

Immunoglobulin E (IgE) antibodies are well known for their role in mediating allergic reactions, and their powerful effector functions activated through binding to Fc receptors FcεRI and FcεRII/CD23. Structural studies of IgE-Fc alone, and when bound to these receptors, surprisingly revealed not only an acutely bent Fc conformation, but also subtle allosteric communication between the two distant receptor-binding sites. The ability of IgE-Fc to undergo more extreme conformational changes emerged from structures of complexes with anti-IgE antibodies, including omalizumab, in clinical use for allergic disease; flexibility is clearly critical for IgE function, but may also be exploited by allosteric interference to inhibit IgE activity for therapeutic benefit. In contrast, the power of IgE may be harnessed to target cancer. Efforts to improve the effector functions of therapeutic antibodies for cancer have almost exclusively focussed on IgG1 and IgG4 subclasses, but IgE offers an extremely high affinity for FcεRI receptors on immune effector cells known to infiltrate solid tumours. Furthermore, while tumour-resident inhibitory Fc receptors can modulate the effector functions of IgG antibodies, no inhibitory IgE Fc receptors are known to exist. The development of tumour antigen-specific IgE antibodies may therefore provide an improved immune functional profile and enhanced anti-cancer efficacy. We describe proof-of-concept studies of IgE immunotherapies against solid tumours, including a range of in vitro and in vivo evaluations of efficacy and mechanisms of action, as well as ex vivo and in vivo safety studies. The first anti-cancer IgE antibody, MOv18, the clinical translation of which we discuss herein, has now reached clinical testing, offering great potential to direct this novel therapeutic modality against many other tumour-specific antigens. This review highlights how our understanding of IgE structure and function underpins these exciting clinical developments.

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