PMID- 34870820
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 2421
DP  - 2022
TI  - Engineering IgG1 Fc Domains That Activate the Complement System.
PG  - 187-200
LID - 10.1007/978-1-0716-1944-5_13 [doi]
AB  - Fc-mediated effector functions are important for the clearance of pathologic 
      cells by therapeutic IgG antibodies through two mechanisms: via the activation of 
      the classical complement pathway and through the binding to Fcgamma receptors (FcgammaRs) 
      which mediate clearance of targeted cells by antibody-dependent cellular 
      cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) by 
      effector cells such as macrophages, NK cells, and other leukocytes subsets. 
      Complement activation results in direct cell killing through the formation of the 
      membrane attack complex (MAC, complement-dependent cytotoxicity or CDC) and in 
      the deposition of complement opsonins on pathogen surfaces. The latter are 
      recognized by complement receptors on effector cells in turn triggering 
      complement-dependent cell cytotoxicity and phagocytosis (CDCC and CDCP, 
      respectively). Little is known about the role of CDCC and CDCP on therapeutic 
      antibody function because on the one hand, IgG isotype antibodies bind to both 
      FcgammaR and C1q to activate the complement pathway, and on the other, immune cells 
      express complement receptor as well as FcgammaRs. We engineered IgG1 Fc domains that 
      bind with high affinity to C1q but have very little or no binding to FcgammaR. To 
      this end, we employed display of IgG in E. coli (which lack protein glycosylation 
      machinery) for the screening of very large libraries (>2 x 10(9)) of randomly 
      mutated human Fc domains to isolate Fc variants that bind to C1q. Herein we 
      introduce and describe the method.
CI  - (c) 2022. Springer Science+Business Media, LLC, part of Springer Nature.
FAU - Lee, Chang-Han
AU  - Lee CH
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, South Korea. chlee-antibody@snu.ac.kr.
FAU - Delidakis, George
AU  - Delidakis G
AD  - Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - 0 (Receptors, IgG)
RN  - 80295-33-6 (Complement C1q)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Complement C1q
MH  - Complement System Proteins
MH  - Escherichia coli
MH  - Humans
MH  - Immunoglobulin Fc Fragments/genetics
MH  - Immunoglobulin G/genetics/*immunology
MH  - Protein Engineering
MH  - Receptors, Fc
MH  - Receptors, IgG/genetics
OTO - NOTNLM
OT  - Aglycosylated Fc domain
OT  - Antibody engineering
OT  - Bacterial surface display
OT  - Complement
OT  - Fc engineering
EDAT- 2021/12/07 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/12/06 12:31
PHST- 2021/12/06 12:31 [entrez]
PHST- 2021/12/07 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
AID - 10.1007/978-1-0716-1944-5_13 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2022;2421:187-200. doi: 10.1007/978-1-0716-1944-5_13.