Journal ArticleDOI
Human antibody-Fc receptor interactions illuminated by crystal structures.
Jenny M. Woof,Dennis R. Burton +1 more
TLDR
The structural information that is emerging on three human immunoglobulin classes and their FcRs is reviewed, including an understanding of the antibody conformational adjustments that are required to bring effector cell and target cell membranes sufficiently close for efficient killing and signal transduction to occur.Abstract:
Immunoglobulins couple the recognition of invading pathogens with the triggering of potent effector mechanisms for pathogen elimination. Different immunoglobulin classes trigger different effector mechanisms through interaction of immunoglobulin Fc regions with specific Fc receptors (FcRs) on immune cells. Here, we review the structural information that is emerging on three human immunoglobulin classes and their FcRs. New insights are provided, including an understanding of the antibody conformational adjustments that are required to bring effector cell and target cell membranes sufficiently close for efficient killing and signal transduction to occur. The results might also open up new possibilities for the design of therapeutic antibodies.read more
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Journal ArticleDOI
Engineered antibody fragments and the rise of single domains
Philipp Holliger,Peter J Hudson +1 more
TL;DR: There is tremendous potential for all antibody fragments either as robust diagnostic reagents, or as nonimmunogenic in vivo biopharmaceuticals with superior biodistribution and blood clearance properties.
Journal ArticleDOI
Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses
Pierre Bruhns,Pierre Bruhns,Bruno Iannascoli,Bruno Iannascoli,Patrick England,Patrick England,David A. Mancardi,David A. Mancardi,Nadine Fernandez,Sylvie Jorieux,Marc Daëron,Marc Daëron +11 more
TL;DR: The results document how hFcgammaR specificity and affinity may account for the biological activities of antibodies and highlight the role of specific hF cgammaRs in the therapeutic and pathogenic effects of antibodies in disease.
Journal ArticleDOI
Glycosylation as a strategy to improve antibody-based therapeutics
TL;DR: Current knowledge of methods and avenues for their exploitation in the clinic are summarized, which allow the production of rMAbs bearing pre-selected oligosaccharides — glycoforms — to provide maximum efficacy for a given disease indication.
Journal ArticleDOI
Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting
TL;DR: How direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large-scale application of DC-based vaccination therapies is discussed.
Journal ArticleDOI
The function of immunoglobulin A in immunity
Jenny M. Woof,Michael A. Kerr +1 more
TL;DR: Current understanding of the roles played by IgA in both health and disease is detailed, with a focus on the role of mucosal surfaces.
References
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Journal ArticleDOI
Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular Toxicity
Robert L. Shields,Jadine Lai,Rodney G. Keck,Lori Y. O'Connell,Kyu Hong,Y. Gloria Meng,Stefanie Weikert,Leonard G. Presta +7 more
TL;DR: Antibody-dependent cellular cytot toxicity assays using purified peripheral blood monocytes or natural killer cells from several donors showed enhanced cytotoxicity, especially evident at lower antibody concentrations.
Journal ArticleDOI
The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity.
Toyohide Shinkawa,Kazuyasu Nakamura,Naoko Yamane,Emi Shoji-Hosaka,Yutaka Kanda,Mikiko Sakurada,Kazuhisa Uchida,Hideharu Anazawa,Mitsuo Satoh,Motoo Yamasaki,Nobuo Hanai,Kenya Shitara +11 more
TL;DR: The results indicate that the lack of fucosylation of IgG1 has the most critical role in enhancement of ADCC, although several reports have suggested the importance of Gal or bisecting GlcNAc and provide important information to produce the effective therapeutic antibody.
Journal ArticleDOI
Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution.
TL;DR: The model of human Fc fragment was refined at 2.9-A resolution and the R value of the model is 0.24, with strong arguments that contact 1 is the fragment B-Fc contact formed in solution under physiological conditions, while contact 2 is a crystal contact.
Journal ArticleDOI
A new member of the immunoglobulin superfamily--CTLA-4.
Jean-François Brunet,François Denizot,Marie-Françoise Luciani,Magali Roux-Dosseto,Magali Roux-Dosseto,Marie Suzan,Marie-Geneviève Mattei,Pierre Golstein +7 more
TL;DR: CTLA-4 is mainly expressed in activated lymphocytes and is coinduced with T-cell-mediated cytotoxicity in inducible models of this process and could encode a 223-amino-acid protein clearly belonging to the immunoglobulin superfamily.