Nanoscale spatial dependence of avidity in an IgG1 antibody

Abstract Antibodies are secreted proteins that are crucial to recognition of pathogens by the immune system and are also efficient pharmaceuticals. The affinity and specificity of target recognition can increase remarkably through avidity effects, when the antibody can bind a multivalent antigen thr...

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Autores principales:	Agnieszka Jendroszek, Magnus Kjaergaard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b8a3aa37c394da7b6321624c51f9191
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spelling	oai:doaj.org-article:7b8a3aa37c394da7b6321624c51f91912021-12-02T17:39:53ZNanoscale spatial dependence of avidity in an IgG1 antibody10.1038/s41598-021-92280-22045-2322https://doaj.org/article/7b8a3aa37c394da7b6321624c51f91912021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92280-2https://doaj.org/toc/2045-2322Abstract Antibodies are secreted proteins that are crucial to recognition of pathogens by the immune system and are also efficient pharmaceuticals. The affinity and specificity of target recognition can increase remarkably through avidity effects, when the antibody can bind a multivalent antigen through more than one epitope simultaneously. A key goal of antibody engineering is thus to optimize avidity, but little is known about the nanoscale spatial dependence of avidity in antibodies. Here, we develop a set of anti-parallel coiled-coils spanning from 7 to 20 nm and validate their structure using biophysical techniques. We use the coiled-coils to control the spacing between two epitopes, and measure how antigen spacing affects the stability of the bivalent antibody:antigen complex. We find a maximal avidity enhancement at a spacing of 13 nm. In contrast to recent studies, we find the avidity to be relatively insensitive to epitope spacing near the avidity maximum as long as it is within the spatial tolerance of the antibody. We thus only see a ~ twofold variation of avidity in the range from 7 to 20 nm. The coiled-coil systems developed here may prove a useful protein nanocaliper for profiling the spatial tolerance and avidity profile of bispecific antibodies.Agnieszka JendroszekMagnus KjaergaardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agnieszka Jendroszek Magnus Kjaergaard Nanoscale spatial dependence of avidity in an IgG1 antibody
description	Abstract Antibodies are secreted proteins that are crucial to recognition of pathogens by the immune system and are also efficient pharmaceuticals. The affinity and specificity of target recognition can increase remarkably through avidity effects, when the antibody can bind a multivalent antigen through more than one epitope simultaneously. A key goal of antibody engineering is thus to optimize avidity, but little is known about the nanoscale spatial dependence of avidity in antibodies. Here, we develop a set of anti-parallel coiled-coils spanning from 7 to 20 nm and validate their structure using biophysical techniques. We use the coiled-coils to control the spacing between two epitopes, and measure how antigen spacing affects the stability of the bivalent antibody:antigen complex. We find a maximal avidity enhancement at a spacing of 13 nm. In contrast to recent studies, we find the avidity to be relatively insensitive to epitope spacing near the avidity maximum as long as it is within the spatial tolerance of the antibody. We thus only see a ~ twofold variation of avidity in the range from 7 to 20 nm. The coiled-coil systems developed here may prove a useful protein nanocaliper for profiling the spatial tolerance and avidity profile of bispecific antibodies.
format	article
author	Agnieszka Jendroszek Magnus Kjaergaard
author_facet	Agnieszka Jendroszek Magnus Kjaergaard
author_sort	Agnieszka Jendroszek
title	Nanoscale spatial dependence of avidity in an IgG1 antibody
title_short	Nanoscale spatial dependence of avidity in an IgG1 antibody
title_full	Nanoscale spatial dependence of avidity in an IgG1 antibody
title_fullStr	Nanoscale spatial dependence of avidity in an IgG1 antibody
title_full_unstemmed	Nanoscale spatial dependence of avidity in an IgG1 antibody
title_sort	nanoscale spatial dependence of avidity in an igg1 antibody
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7b8a3aa37c394da7b6321624c51f9191
work_keys_str_mv	AT agnieszkajendroszek nanoscalespatialdependenceofavidityinanigg1antibody AT magnuskjaergaard nanoscalespatialdependenceofavidityinanigg1antibody
_version_	1718379771985920000

Nanoscale spatial dependence of avidity in an IgG1 antibody

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