PMID- 19074274
OWN - NLM
STAT- MEDLINE
DCOM- 20090127
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 51
DP  - 2008 Dec 23
TI  - Aglycosylated immunoglobulin G1 variants productively engage activating Fc 
      receptors.
PG  - 20167-72
LID - 10.1073/pnas.0809257105 [doi]
AB  - Immunoglobulin G plays a vital role in adaptive immunity and antibody-based 
      therapy through engagement of its Fc region by the Fc gamma receptors (Fc 
      gammaRs) on immune cells. In addition to specific protein-protein contacts, 
      N-linked glycosylation of the IgG Fc has been thought to be essential for the 
      recognition of Fc by Fc gammaR. This requirement for the N-linked glycan has 
      limited biomanufacture of therapeutic antibodies by restricting it to mammalian 
      expression systems. We report here aglycosylated Fc domain variants that maintain 
      engagement to Fc gammaRs, both in vitro and in vivo, demonstrating that Fc 
      glycosylation is not strictly required for the activation of immune cells by IgG. 
      These variants provide insight into how the N-linked glycan is used biologically 
      in the recognition of Fc by Fc gammaRs, as well as represent a step toward the 
      production in alternative expression systems of antibody-based therapeutics 
      capable of eliciting immune effector functions.
FAU - Sazinsky, Stephen L
AU  - Sazinsky SL
AD  - Department of Biological Engineering, Massachusetts Institute of Technology, 77 
      Massachusetts Avenue, Cambridge, MA 02139, USA.
FAU - Ott, Rene G
AU  - Ott RG
FAU - Silver, Nathaniel W
AU  - Silver NW
FAU - Tidor, Bruce
AU  - Tidor B
FAU - Ravetch, Jeffrey V
AU  - Ravetch JV
FAU - Wittrup, K Dane
AU  - Wittrup KD
LA  - eng
GR  - R01 CA096504/CA/NCI NIH HHS/United States
GR  - R01 GM065418/GM/NIGMS NIH HHS/United States
GR  - T32 GM008334/GM/NIGMS NIH HHS/United States
GR  - CA96504/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081212
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Genetic Variation
MH  - Glycosylation
MH  - Immunoglobulin G/*genetics/immunology
MH  - Protein Binding/genetics/immunology
MH  - Receptors, Fc/*immunology
MH  - Receptors, IgG/immunology
PMC - PMC2629253
COIS- The authors declare no conflict of interest.
EDAT- 2008/12/17 09:00
MHDA- 2009/01/28 09:00
PMCR- 2009/06/23
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/01/28 09:00 [medline]
PHST- 2009/06/23 00:00 [pmc-release]
AID - 0809257105 [pii]
AID - 5384 [pii]
AID - 10.1073/pnas.0809257105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20167-72. doi: 
      10.1073/pnas.0809257105. Epub 2008 Dec 12.