PMID- 31632959
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220727
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 7
DP  - 2019
TI  - In Planta Glycan Engineering and Functional Activities of IgE Antibodies.
PG  - 242
LID - 10.3389/fbioe.2019.00242 [doi]
LID - 242
AB  - Human immunoglobulin E (IgE) is the most extensively glycosylated antibody 
      isotype so glycans attached to the seven N-glycosites (NGS) in its Fab and Fc 
      domains may modulate its functions. However, targeted modification of glycans in 
      multiply glycosylated proteins remains a challenge. Here, we applied an in vivo 
      approach that allows the manipulation of IgE N-glycans, using a trastuzumab 
      equivalent IgE (HER2-IgE) as a model. Taking advantage of plant inherent 
      features, i.e., synthesis of largely homogeneous complex N-glycans and 
      susceptibility to glycan engineering, we generated targeted glycoforms of 
      HER2-IgE largely resembling those found in serum IgE. Plant-derived HER2-IgE 
      exhibited N-glycans terminating with GlcNAc, galactose or sialic acid, lacking, 
      or carrying core fucose and xylose. We were able to not only modulate the five 
      NGSs naturally decorated with complex N-glycans, but to also induce targeted 
      glycosylation at the usually unoccupied NGS6, thus increasing the overall 
      glycosylation content of HER2-IgE. Recombinant human cell-derived HER2-IgE 
      exhibited large N-glycan heterogeneity. All HER2-IgE variants demonstrated 
      glycosylation-independent binding to the target antigen and the high affinity 
      receptor FcepsilonRI, and subsequent similar capacity to trigger mast cell 
      degranulation. In contrast, binding to the low affinity receptor CD23 (FcepsilonRII) 
      was modulated by the glycan profile, with increased binding to IgE variants with 
      glycans terminating with GlcNAc residues. Here we offer an efficient in planta 
      approach to generate defined glycoforms on multiply glycosylated IgE, allowing 
      the precise exploration of glycosylation-dependent activities.
CI  - Copyright (c) 2019 Montero-Morales, Maresch, Crescioli, Castilho, Ilieva, Mele, 
      Karagiannis, Altmann and Steinkellner.
FAU - Montero-Morales, Laura
AU  - Montero-Morales L
AD  - Department of Applied Genetics and Cell Biology, University of Natural Resources 
      and Life Sciences, Vienna, Austria.
FAU - Maresch, Daniel
AU  - Maresch D
AD  - Department of Chemistry, University of Natural Resources and Life Sciences, 
      Vienna, Austria.
FAU - Crescioli, Silvia
AU  - Crescioli S
AD  - School of Basic and Medical Biosciences, King's College London, St. John's 
      Institute of Dermatology, Guy's Hospital, London, United Kingdom.
FAU - Castilho, Alexandra
AU  - Castilho A
AD  - Department of Applied Genetics and Cell Biology, University of Natural Resources 
      and Life Sciences, Vienna, Austria.
FAU - Ilieva, Kristina M
AU  - Ilieva KM
AD  - School of Basic and Medical Biosciences, King's College London, St. John's 
      Institute of Dermatology, Guy's Hospital, London, United Kingdom.
AD  - Breast Cancer Now Research Unit, Guy's Cancer Centre, School of Cancer and 
      Pharmaceutical Sciences, King's College London, London, United Kingdom.
FAU - Mele, Silvia
AU  - Mele S
AD  - School of Basic and Medical Biosciences, King's College London, St. John's 
      Institute of Dermatology, Guy's Hospital, London, United Kingdom.
FAU - Karagiannis, Sophia N
AU  - Karagiannis SN
AD  - School of Basic and Medical Biosciences, King's College London, St. John's 
      Institute of Dermatology, Guy's Hospital, London, United Kingdom.
AD  - Breast Cancer Now Research Unit, Guy's Cancer Centre, School of Cancer and 
      Pharmaceutical Sciences, King's College London, London, United Kingdom.
FAU - Altmann, Friedrich
AU  - Altmann F
AD  - Department of Chemistry, University of Natural Resources and Life Sciences, 
      Vienna, Austria.
FAU - Steinkellner, Herta
AU  - Steinkellner H
AD  - Department of Applied Genetics and Cell Biology, University of Natural Resources 
      and Life Sciences, Vienna, Austria.
LA  - eng
GR  - MR/L023091/1/MRC_/Medical Research Council/United Kingdom
GR  - P 28673/FWF_/Austrian Science Fund FWF/Austria
GR  - W 1224/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
DEP - 20190925
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC6781838
OTO - NOTNLM
OT  - IgE
OT  - antibodies
OT  - glycan engineering
OT  - glycosylation
OT  - plants
EDAT- 2019/10/22 06:00
MHDA- 2019/10/22 06:01
PMCR- 2019/01/01
CRDT- 2019/10/22 06:00
PHST- 2019/08/14 00:00 [received]
PHST- 2019/09/12 00:00 [accepted]
PHST- 2019/10/22 06:00 [entrez]
PHST- 2019/10/22 06:00 [pubmed]
PHST- 2019/10/22 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fbioe.2019.00242 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2019 Sep 25;7:242. doi: 10.3389/fbioe.2019.00242. 
      eCollection 2019.