Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses

Blundell, Pat ORCID: https://orcid.org/0000-0003-3386-5660, Lu, Dongli, Dell, Anne, Haslam, Stuart and Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296 (2020) 'Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses'. Journal of Immunology, Vol 204, Issue 4, pp. 1022-1034.

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Abstract

Abs are glycoproteins that carry a conserved N-linked carbohydrate attached to the Fc whose presence and fine structure profoundly impacts on their in vivo immunogenicity, pharmacokinetics, and functional attributes. The host cell line used to produce IgG has a major impact on this glycosylation, as different systems express different glycosylation enzymes and transporters that contribute to the specificity and heterogeneity of the final IgG-Fc glycosylation profile. In this study, we compare two panels of glycan-adapted IgG1-Fc mutants expressed in either the human endothelial kidney 293-F or Chinese hamster ovary–K1 systems. We show that the types of N-linked glycans between matched pairs of Fc mutants vary greatly and in particular, with respect, to sialylation. These cell line effects on glycosylation profoundly influence the ability of the engineered Fcs to interact with either human or pathogen receptors. For example, we describe Fc mutants that potently disrupted influenza B–mediated agglutination of human erythrocytes when expressed in Chinese hamster ovary–K1, but not in human endothelial kidney 293-F cells.

Item Type:	Article
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QV Pharmacology > QV 38 Drug action. QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole. WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 515 Human influenza
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.4049/jimmunol.1901145
Depositing User:	Cathy Waldron
Date Deposited:	07 Jan 2020 16:23
Last Modified:	14 Feb 2020 16:36
URI:	https://archive.lstmed.ac.uk/id/eprint/13447

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