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

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


    J Immunol. 2020 Jan 6. pii: ji1901145. doi: 10.4049/jimmunol.1901145. [Epub ahead of print] Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses.

    Blundell PA1, Lu D2, Dell A2, Haslam S2, Pleass RJ3.
    Author information

    1 Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom; and. 2 Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom. 3 Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom; and richard.pleass@lstmed.ac.uk.

    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 plays a major role in 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.
    Copyright ? 2020 The Authors.


    PMID: 31907284 DOI: 10.4049/jimmunol.1901145

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