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المؤلفون: A. Robin Temming, Gillian Dekkers, Ninotska I. L. Derksen, Fleur S. van de Bovenkamp, Theo Rispens, H. Rosina Plomp, Manfred Wuhrer, Gestur Vidarsson, Arthur E. H. Bentlage, Zoltan Szittner
المصدر: Scientific Reports, Vol 10, Iss 1, Pp 1-1 (2020)
مصطلحات موضوعية: Multidisciplinary, business.industry, Computer science, Published Erratum, lcsh:R, MEDLINE, lcsh:Medicine, computer.software_genre, lcsh:Q, Artificial intelligence, business, lcsh:Science, computer, Natural language processing
الوصف: The original version of this Article contained errors in the Reference list. Reference 26 was incorrectly listed as reference 48, and reference 27 was incorrectly listed as reference 31. As a result, the original references 26–30 are now listed as references 28–32, and references 32–47 are now listed as references 33–48. This has been corrected in both the HTML and PDF versions of this Article.
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المؤلفون: Masja de Haas, Yixian Zhao, Nigel M. Stapleton, Stefania P. Bjarnarson, Ruurd C. Verheul, Inger Sandlie, Ingileif Jonsdottir, Annette M. Stemerding, Jan Terje Andersen, Jorrit Gerritsen, Gestur Vidarsson, C. Ellen van der Schoot, Marion Kleijer
المساهمون: Landsteiner Laboratory, Clinical Haematology
المصدر: Nature Communications
Nature communications, 2. Nature Publishing Groupمصطلحات موضوعية: media_common.quotation_subject, General Physics and Astronomy, chemical and pharmacologic phenomena, Receptors, Fc, Biology, Arginine, complex mixtures, Binding, Competitive, General Biochemistry, Genetics and Molecular Biology, Competition (biology), Article, Pneumococcal Infections, 03 medical and health sciences, Mice, 0302 clinical medicine, Neonatal Fc receptor, Agammaglobulinemia, Cell Line, Tumor, parasitic diseases, Animals, Humans, Histidine, Molecular Targeted Therapy, 030304 developmental biology, media_common, 0303 health sciences, Multidisciplinary, Histocompatibility Antigens Class I, Half-life, Antibodies, Monoclonal, General Chemistry, Hydrogen-Ion Concentration, Molecular biology, 3. Good health, Cell biology, Disease Models, Animal, Protein Transport, Streptococcus pneumoniae, Amino Acid Substitution, Mediated transport, Immunoglobulin G, Mutation (genetic algorithm), 030215 immunology, Half-Life, Protein Binding
الوصف: Human IgG3 displays the strongest effector functions of all IgG subclasses but has a short half-life for unresolved reasons. Here we show that IgG3 binds to IgG-salvage receptor (FcRn), but that FcRn-mediated transport and rescue of IgG3 is inhibited in the presence of IgG1 due to intracellular competition between IgG1 and IgG3. We reveal that this occurs because of a single amino acid difference at position 435, where IgG3 has an arginine instead of the histidine found in all other IgG subclasses. While the presence of R435 in IgG increases binding to FcRn at neutral pH, it decreases binding at acidic pH, affecting the rescue efficiency—but only in the presence of H435–IgG. Importantly, we show that in humans the half-life of the H435-containing IgG3 allotype is comparable to IgG1. H435–IgG3 also gave enhanced protection against a pneumococcal challenge in mice, demonstrating H435–IgG3 to be a candidate for monoclonal antibody therapies.
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
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