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  • 1
    Publication Date: 2018-02-16
    Description: Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo–electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1–immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1r 2 s 2 proteases and tilting C1q’s cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces.
    Keywords: Biochemistry, Immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-03-27
    Description: The promise of bispecific antibodies (bsAbs) to yield more effective therapeutics is well recognized; however, the generation of bsAbs in a practical and cost-effective manner has been a formidable challenge. Here we present a technology for the efficient generation of bsAbs with normal IgG structures that is amenable to both...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2007-09-18
    Description: Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Neut Kolfschoten, Marijn -- Schuurman, Janine -- Losen, Mario -- Bleeker, Wim K -- Martinez-Martinez, Pilar -- Vermeulen, Ellen -- den Bleker, Tamara H -- Wiegman, Luus -- Vink, Tom -- Aarden, Lucien A -- De Baets, Marc H -- van de Winkel, Jan G J -- Aalberse, Rob C -- Parren, Paul W H I -- New York, N.Y. -- Science. 2007 Sep 14;317(5844):1554-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sanquin Research-AMC Landsteiner Laboratory, Department of Immunopathology, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17872445" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Antibodies, Bispecific/immunology ; Antibodies, Monoclonal/immunology ; Antigens, CD20/immunology ; Antigens, Plant ; Autoantibodies/immunology ; Glycoproteins/immunology ; Humans ; Immunoglobulin Constant Regions/chemistry ; Immunoglobulin Fab Fragments/*chemistry/*immunology/metabolism ; Immunoglobulin G/*chemistry/*immunology/metabolism ; Immunoglobulin Heavy Chains ; Macaca mulatta ; Mice ; Mutation ; Myasthenia Gravis, Autoimmune, Experimental/immunology/prevention & control ; Protein Processing, Post-Translational ; Receptor, Epidermal Growth Factor/immunology ; Receptors, Cholinergic/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-03-15
    Description: Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250092/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diebolder, Christoph A -- Beurskens, Frank J -- de Jong, Rob N -- Koning, Roman I -- Strumane, Kristin -- Lindorfer, Margaret A -- Voorhorst, Marleen -- Ugurlar, Deniz -- Rosati, Sara -- Heck, Albert J R -- van de Winkel, Jan G J -- Wilson, Ian A -- Koster, Abraham J -- Taylor, Ronald P -- Saphire, Erica Ollmann -- Burton, Dennis R -- Schuurman, Janine -- Gros, Piet -- Parren, Paul W H I -- AI055332/AI/NIAID NIH HHS/ -- AI084817/AI/NIAID NIH HHS/ -- R01 AI055332/AI/NIAID NIH HHS/ -- R37 AI055332/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1260-3. doi: 10.1126/science.1248943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626930" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/*immunology ; *Complement Activation ; Complement C1/*immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology ; Immunoglobulin G/*chemistry/immunology ; Liposomes ; Protein Conformation ; Protein Multimerization
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chemical Physics Letters 73 (1980), S. 429-432 
    ISSN: 0009-2614
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 19 (1937), S. 273-355 
    ISSN: 1573-6857
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Antonie van Leeuwenhoek 61 (1992), S. 43-50 
    ISSN: 1572-9699
    Keywords: leptospires ; muskrats ; Ondatra zibethicus ; The Netherlands ; grippotyphosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Leptospires were isolated from 24 of 327 (7%) muskrats (Ondatra zibethicus) caught in The Netherlands. All isolates were identified asLeptospira interrogans. One isolate was typed as serovarcopenhageni in the Icterohaemorrhagiae serogroup, one as serovarlora in the Australis serogroup. Twenty-one isolates showed a close relationship with serovarsgrippotyphosa, valbuzzi, muelleri andratnapura from the Grippotyphosa serogroup. One isolate was lost. Sera from 196 muskrats were examined by the microscopic agglutination test. Forty-five (23%) sera reacted positively (titers≧1: 160), 42 (21%) of these 45 sera to Grippotyphosa and 3 (2%) to Sejroe serogroup antigens. This is the first report of serological and cultural evidence of leptospira infection in muskrats in The Netherlands.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Plant and soil 22 (1965), S. 352-374 
    ISSN: 1573-5036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Combinations of three grades of density of topsoil and of subsoil in artificial profiles have been used to study the influence of soil density on growth of the roots of oats. The soil was humous sand. The development of roots proved better the less compact the soil is. In the very dense soil rootgrowth was markedly reduced. It is likely that mechanical resistance is the only reason for the restriction of the growth hereby. Whereas a moderate growth of roots was possible even in the most densely packed soil, such a dense subsoil could absolutely not been penetrated by roots coming from a loose topsoil. This is presumably not due to a lack of support in the loose soil, but to an insufficient osmotic pressure in the roots. The hampered rootgrowth in compacted soil limited the uptake of water and nutrients and hereby reduced the development of the tops of plants.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-5036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Spraying young winter rye plants with 4,6-dinitro-o-cresol (DNOC), as a contact herbicide, initially depressed the growth rate of the plants although this subsequently increased until ultimately the yield of plant material was greater than achieved by the control plants, also apart from the herbicidal effect of the treatment. It was observed that the growth rate of the roots of the treated plants recovered sooner than did the growth rate of the aerial parts. Ultimately a greater root dry weight was produced by the treated plants than by the control plants. This was achieved before the dry weights of the aerial parts of the treated plants equalled those of the untreated plants. The shoot/root ratio of the treated plants was lower than that of the control plants and the roots of the treated plants survived longer in the deeper layers of the soil than did those of the control plants. It is suggested that the subsequent increase in shoot growth in the treated plants may be a consequence of increased uptake of nutrients from the soil by a more vigorous root system. It is concluded that the increase in root growth which follows the initial depression, after treatment of the plants with DNOC, may be due to factors within rather than outside the roots.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Plant and soil 6 (1955), S. 373-381 
    ISSN: 1573-5036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Several investigators have published methods for the preservation of soil profiles by treating them with definite organic compounds. In these no data are recorded as to the development of the crop roots in the preserved profiles. In this article a modified technique is described for preserving soil profiles and their root systems simultaneously.
    Type of Medium: Electronic Resource
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