Neisseria meningitidis is a Gram-negative bacterium capable of causing deadly invasive disease. Two recently developed vaccines against N. meningitidis serogroup B include recombinant factor H binding protein (fHbp), a surface protein that meningococci use to evade the host immune system. Many anti-fHbp monoclonal antibodies (mAbs) produced against fHbp fail to trigger complement-mediated bacteriolysis when used alone in vitro, but are highly synergistic and bactericidal when used in combination. This opened the door to defining the structural basis by which mAbs activate complement synergistically when binding to different epitopes on the same antigen, a story that is told by Malito et al. in a recent issue of the Biochemical Journal. Using two separate crystal structures of fHbp bound to Fabs from synergistic mAbs, they were able to model the structure of both full length antibodies bound simultaneously to fHbp. This revealed that the bound antibodies orient their Fc domains 115–130 Å apart, a distance that is compatible with multivalent C1q binding. The need for a precise orientation of Fc domains in order to efficiently activate effector functions is an emerging theme across multiple fields, and its implications could have broad impacts on vaccinology and immunotherapy.
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February 2017
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Cover Image
Docking simulation predicts that the binding of CD81 extracellular domain-2 (EC2) to the RGD-binding site of integrin alphaVbeta3. CD81 EC2 (in red), integrin alphaV (in light green), and integrin beta3 (in purple). Please see pp. 589–596 for more information. Image provided by Yoshikazu Takada.
Commentary|
February 03 2017
Getting oriented with antibodies
Erik H. Klontz;
Erik H. Klontz
1Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
2Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
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Eric J. Sundberg
1Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
2Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
3Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
Correspondence: Eric J. Sundberg (esundberg@ihv.umaryland.edu)
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Publisher: Portland Press Ltd
Received:
December 05 2016
Revision Received:
December 12 2016
Accepted:
December 14 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (4): 517–519.
Article history
Received:
December 05 2016
Revision Received:
December 12 2016
Accepted:
December 14 2016
Connected Content
Citation
Erik H. Klontz, Eric J. Sundberg; Getting oriented with antibodies. Biochem J 15 February 2017; 474 (4): 517–519. doi: https://doi.org/10.1042/BCJ20160996
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