PMID- 33310702
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20210830
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 296
DP  - 2021 Jan-Jun
TI  - Fc gamma receptor IIIa/CD16a processing correlates with the expression of 
      glycan-related genes in human natural killer cells.
PG  - 100183
LID - S0021-9258(20)00179-9 [pii]
LID - 10.1074/jbc.RA120.015516 [doi]
LID - 100183
AB  - Many therapeutic monoclonal antibodies require binding to Fc gamma receptors (FcgammaRs) 
      for full effect and increasing the binding affinity increases efficacy. 
      Preeminent among the five activating human FcgammaRs is FcgammaRIIIa/CD16a expressed by 
      natural killer (NK) cells. CD16a is heavily processed, and recent reports 
      indicate that the composition of the five CD16a asparagine(N)-linked 
      carbohydrates (glycans) impacts affinity. These observations indicate that 
      specific manipulation of CD16a N-glycan composition in CD16a-expressing effector 
      cells including NK cells may improve treatment efficacy. However, it is unclear 
      if modifying the expression of select genes that encode processing enzymes in 
      CD16a-expressing effector cells is sufficient to affect N-glycan composition. We 
      identified substantial processing differences using a glycoproteomics approach by 
      comparing CD16a isolated from two NK cell lines, NK92 and YTS, with CD16a 
      expressed by HEK293F cells and previous reports of CD16a from primary NK cells. 
      Gene expression profiling by RNA-Seq and qRT-PCR revealed expression levels for 
      glycan-modifying genes that correlated with CD16a glycan composition. These 
      results identified a high degree of variability between the processing of the 
      same human protein by different human cell types. N-glycan processing correlated 
      with the expression of glycan-modifying genes and thus explained the substantial 
      differences in CD16a processing by NK cells of different origins.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Patel, Kashyap R
AU  - Patel KR
AD  - Department of Biochemistry, Biophysics and Molecular Biology, Iowa State 
      University, Ames, Iowa, USA.
FAU - Rodriguez Benavente, Maria C
AU  - Rodriguez Benavente MC
AD  - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, 
      Georgia, USA.
FAU - Lorenz, W Walter
AU  - Lorenz WW
AD  - Georgia Genomics and Bioinformatics Core and Institute of Bioinformatics, 
      University of Georgia, Athens, Georgia, USA.
FAU - Mace, Emily M
AU  - Mace EM
AD  - Department of Pediatrics, Columbia University Irving Medical Center, New York, 
      New York, USA.
FAU - Barb, Adam W
AU  - Barb AW
AD  - Department of Biochemistry, Biophysics and Molecular Biology, Iowa State 
      University, Ames, Iowa, USA; Department of Biochemistry and Molecular Biology, 
      University of Georgia, Athens, Georgia, USA; Complex Carbohydrate Research 
      Center, University of Georgia, Athens, Georgia, USA. Electronic address: 
      abarb@uga.edu.
LA  - eng
GR  - R01 GM115489/GM/NIGMS NIH HHS/United States
GR  - R21 AI142122/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201216
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Glycopeptides)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Cell Line
MH  - Glycopeptides/analysis/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Killer Cells, Natural/chemistry/*metabolism
MH  - Models, Molecular
MH  - Polysaccharides/*genetics
MH  - Receptors, IgG/chemistry/*metabolism
MH  - *Transcriptome
PMC - PMC7948478
OTO - NOTNLM
OT  - Fc-gamma receptor
OT  - N-linked glycosylation
OT  - NK-92
OT  - YTS
OT  - gene expression
OT  - glycoproteomics
OT  - natural killer cells (NK cells)
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2020/12/15 06:00
MHDA- 2021/08/31 06:00
PMCR- 2020/12/16
CRDT- 2020/12/14 10:42
PHST- 2020/08/04 00:00 [received]
PHST- 2020/12/03 00:00 [revised]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2020/12/14 10:42 [entrez]
PHST- 2020/12/16 00:00 [pmc-release]
AID - S0021-9258(20)00179-9 [pii]
AID - 100183 [pii]
AID - 10.1074/jbc.RA120.015516 [doi]
PST - ppublish
SO  - J Biol Chem. 2021 Jan-Jun;296:100183. doi: 10.1074/jbc.RA120.015516. Epub 2020 
      Dec 16.