PMID- 29960887
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20210109
IS  - 2405-4712 (Print)
IS  - 2405-4720 (Electronic)
IS  - 2405-4712 (Linking)
VI  - 7
IP  - 1
DP  - 2018 Jul 25
TI  - Dissecting FcgammaR Regulation through a Multivalent Binding Model.
PG  - 41-48.e5
LID - S2405-4712(18)30236-9 [pii]
LID - 10.1016/j.cels.2018.05.018 [doi]
AB  - Many immune receptors transduce activation across the plasma membrane through 
      their clustering. With Fcgamma receptors (FcgammaRs), this clustering is driven by 
      binding to antibodies of differing affinities that are in turn bound to 
      multivalent antigen. As a consequence of this activation mechanism, accounting 
      for and rationally manipulating immunoglobulin (Ig)G effector function is 
      complicated by, among other factors, differing affinities between FcgammaR species 
      and changes in the valency of antigen binding. In this study, we show that a 
      model of multivalent receptor-ligand binding can effectively account for the 
      contribution of IgG-FcgammaR affinity and immune complex valency. This model in turn 
      enables us to make specific predictions about the effect of immune complexes of 
      defined composition. In total, these results enable both rational immune complex 
      design for a desired IgG effector function and the deconvolution of effector 
      function by immune complexes.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Robinett, Ryan A
AU  - Robinett RA
AD  - Koch Institute for Integrative Cancer Research, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA.
FAU - Guan, Ning
AU  - Guan N
AD  - Koch Institute for Integrative Cancer Research, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA.
FAU - Lux, Anja
AU  - Lux A
AD  - Division of Genetics, Department of Biology, Friedrich-Alexander-University of 
      Erlangen-Nurnberg, Erlangen 91058, Germany.
FAU - Biburger, Markus
AU  - Biburger M
AD  - Division of Genetics, Department of Biology, Friedrich-Alexander-University of 
      Erlangen-Nurnberg, Erlangen 91058, Germany.
FAU - Nimmerjahn, Falk
AU  - Nimmerjahn F
AD  - Division of Genetics, Department of Biology, Friedrich-Alexander-University of 
      Erlangen-Nurnberg, Erlangen 91058, Germany.
FAU - Meyer, Aaron S
AU  - Meyer AS
AD  - Department of Bioengineering, Jonsson Comprehensive Cancer Center, Eli and Edythe 
      Broad Center of Regenerative Medicine and Stem Cell Research, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: 
      ameyer@asmlab.org.
LA  - eng
GR  - DP5 OD019815/OD/NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180627
PL  - United States
TA  - Cell Syst
JT  - Cell systems
JID - 101656080
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Carrier Proteins)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Antibodies/metabolism/physiology
MH  - Antibodies, Monoclonal/immunology
MH  - Antibody Affinity
MH  - Antigen-Antibody Complex/immunology
MH  - B-Lymphocyte Subsets/metabolism
MH  - CHO Cells
MH  - Carrier Proteins/metabolism
MH  - Cell Membrane/physiology
MH  - Cricetulus
MH  - Humans
MH  - Immune System Phenomena/physiology
MH  - Immunoglobulin Fc Fragments/*chemistry/physiology
MH  - Immunoglobulin G/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Binding/physiology
MH  - Receptors, IgG/*metabolism/physiology
PMC - PMC6062446
MID - NIHMS978165
OTO - NOTNLM
OT  - FcgammaR receptors
OT  - antibodies
OT  - cell specificity
OT  - effector function
OT  - immunology
COIS- Declaration of Interests The authors declare no competing financial interests.
EDAT- 2018/07/02 06:00
MHDA- 2019/10/01 06:00
PMCR- 2019/07/25
CRDT- 2018/07/02 06:00
PHST- 2017/12/04 00:00 [received]
PHST- 2018/03/31 00:00 [revised]
PHST- 2018/05/22 00:00 [accepted]
PHST- 2018/07/02 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/07/02 06:00 [entrez]
PHST- 2019/07/25 00:00 [pmc-release]
AID - S2405-4712(18)30236-9 [pii]
AID - 10.1016/j.cels.2018.05.018 [doi]
PST - ppublish
SO  - Cell Syst. 2018 Jul 25;7(1):41-48.e5. doi: 10.1016/j.cels.2018.05.018. Epub 2018 
      Jun 27.