Effect of posttranslational modifications and subclass on IgG activity: From Immunity to Immunotherapy
Effect of posttranslational modifications and subclass on IgG activity: From Immunity to Immunotherapy
Humoral immune responses are characterized by complex mixtures of polyclonal antibody species varying in their isotype, target epitope specificity and affinity. Posttranslational modifications occurring during antibody production in both the antibody variable and constant domain create further complexity and can modulate antigen specificity and antibody Fc-dependent effector functions, respectively. Finally, modifications of the antibody backbone after secretion may further impact antibody activity. An in-depth understanding of how these posttranslational modifications impact antibody function, especially in the context of individual antibody isotypes and subclasses, is only starting to emerge. Indeed, only a minute proportion of this natural variability in the humoral immune response is currently reflected in therapeutic antibody preparations. In this Review, we summarize recent insights into how IgG subclass and posttranslational modifications impact IgG activity and discuss how these insights may be used to optimize therapeutic antibody development.
1244–1255
Nimmerjahn, Falk
602fe2d2-f100-45fc-8063-c2aadec62e93
Vidarsson, Gestur
e827609d-10dd-4ad0-a97b-ddb323f5c677
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
August 2023
Nimmerjahn, Falk
602fe2d2-f100-45fc-8063-c2aadec62e93
Vidarsson, Gestur
e827609d-10dd-4ad0-a97b-ddb323f5c677
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Nimmerjahn, Falk, Vidarsson, Gestur and Cragg, Mark
(2023)
Effect of posttranslational modifications and subclass on IgG activity: From Immunity to Immunotherapy.
Nature Immunology, 24 (8), .
(doi:10.1038/s41590-023-01544-8).
Abstract
Humoral immune responses are characterized by complex mixtures of polyclonal antibody species varying in their isotype, target epitope specificity and affinity. Posttranslational modifications occurring during antibody production in both the antibody variable and constant domain create further complexity and can modulate antigen specificity and antibody Fc-dependent effector functions, respectively. Finally, modifications of the antibody backbone after secretion may further impact antibody activity. An in-depth understanding of how these posttranslational modifications impact antibody function, especially in the context of individual antibody isotypes and subclasses, is only starting to emerge. Indeed, only a minute proportion of this natural variability in the humoral immune response is currently reflected in therapeutic antibody preparations. In this Review, we summarize recent insights into how IgG subclass and posttranslational modifications impact IgG activity and discuss how these insights may be used to optimize therapeutic antibody development.
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Nimmerjahn_edited
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More information
Accepted/In Press date: 15 May 2023
e-pub ahead of print date: 6 July 2023
Published date: August 2023
Additional Information:
Funding Information:
This work has been funded by grants from the German Research Foundation (TRR305-B02, CRC1181-A07, CRC1526-A07, FOR2886-B2 and FOR2953-P3) and the National Institutes of Health (NIH; U01-AI-148119 and 5U19A/142790-04) to F.N. and by grants from Cancer Research UK (A20537, DRCDDRPGM-Apr2020\100005 and A24721) and NIH (grant UO1AI148153) to M.S.C.
Identifiers
Local EPrints ID: 480832
URI: http://eprints.soton.ac.uk/id/eprint/480832
ISSN: 1529-2908
PURE UUID: 51e83d25-4ee7-4dde-be5d-be12cbc248bb
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Date deposited: 10 Aug 2023 16:34
Last modified: 18 Mar 2024 02:47
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Author:
Falk Nimmerjahn
Author:
Gestur Vidarsson
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