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| http://dx.doi.org/10.1038/cmi.2015.14 | DOI Listing |
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IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action.
Annu Rev Immunol
April 2023
Randall Centre for Cell and Molecular Biophysics and School of Basic and Medical Biosciences, King's College London, London, UK; email:
The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE.
View Article and Find Full Text PDFDirected evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex.
Nat Commun
December 2021
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Antibody drugs exert therapeutic effects via a range of mechanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms. Facilitated dissociation is an additional mechanism where antibody-mediated "disruption" of stable high-affinity macromolecular complexes can potentially enhance therapeutic efficacy. However, this mechanism is not well understood or utilized therapeutically.
View Article and Find Full Text PDFSplit & mix assembly of DNA libraries for ultrahigh throughput on-bead screening of functional proteins.
Nucleic Acids Res
June 2020
Department of Biochemistry, University of Cambridge, 80 Tennis Court Rd, Cambridge CB2 1GA, UK.
Site-saturation libraries reduce protein screening effort in directed evolution campaigns by focusing on a limited number of rationally chosen residues. However, uneven library synthesis efficiency leads to amino acid bias, remedied at high cost by expensive custom synthesis of oligonucleotides, or through use of proprietary library synthesis platforms. To address these shortcomings, we have devised a method where DNA libraries are constructed on the surface of microbeads by ligating dsDNA fragments onto growing, surface-immobilised DNA, in iterative split-and-mix cycles.
View Article and Find Full Text PDFImmunologic mechanisms in asthma.
Semin Immunol
December 2019
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. Electronic address:
Asthma is a chronic airway disease, which affects more than 300 million people. The pathogenesis of asthma exhibits marked heterogeneity with many phenotypes defining visible characteristics and endotypes defining molecular mechanisms. With the evolution of novel biological therapies, patients, who do not-respond to conventional asthma therapy require novel biologic medications, such as anti-IgE, anti-IL-5 and anti-IL4/IL13 to control asthma symptoms.
View Article and Find Full Text PDFPhenotypes/endotypes-driven treatment in asthma.
Curr Opin Allergy Clin Immunol
June 2018
Gazi University School of Medicine, Department of Chest Diseases, Ankara, Turkey.
Purpose Of Review: Target therapy is the necessary step towards personalized medicine. The definition of asthma phenotypes and underlying mechanisms (endotypes) represent a key point in the development of new asthma treatments. Big data analysis, biomarker research and the availability of monoclonal antibodies, targeting specific cytokines is leading to the rapid evolution of knowledge.
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