Impact of Antigen Density on the Binding Mechanism of IgG Antibodies

Abstract The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition me...

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Autores principales: Maya Hadzhieva, Anastas D. Pashov, Srinivas Kaveri, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D. Dimitrov
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/2a9f6eab595e44edb829b92bb61362e7
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spelling oai:doaj.org-article:2a9f6eab595e44edb829b92bb61362e72021-12-02T11:40:32ZImpact of Antigen Density on the Binding Mechanism of IgG Antibodies10.1038/s41598-017-03942-z2045-2322https://doaj.org/article/2a9f6eab595e44edb829b92bb61362e72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03942-zhttps://doaj.org/toc/2045-2322Abstract The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition mechanisms is missing. Here, we analyzed binding kinetics and thermodynamics of six HIV-1 neutralizing antibodies as a function of the surface density of envelope glycoprotein gp120. Antibodies that recognize gp120 with low to moderate binding affinity displayed the most pronounced sensitivity to variation in antigen density, with qualitative and substantial quantitative changes in the energetics of the binding process as revealed by non-equilibrium and equilibrium thermodynamic analyses. In contrast, the recognition of gp120 by the antibodies with the highest affinity was considerably less influenced by variations in antigen density. These data suggest that a lower affinity of antibodies permits higher dynamics during the antigen recognition process, which may have considerable functional repercussions. These findings contribute to a better understanding of the mechanisms of antigen recognition by antibodies. They are also of importance for apprehending the impact of antigen topology on immune-defense functions of antibodies.Maya HadzhievaAnastas D. PashovSrinivas KaveriSébastien Lacroix-DesmazesHugo MouquetJordan D. DimitrovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maya Hadzhieva
Anastas D. Pashov
Srinivas Kaveri
Sébastien Lacroix-Desmazes
Hugo Mouquet
Jordan D. Dimitrov
Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
description Abstract The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition mechanisms is missing. Here, we analyzed binding kinetics and thermodynamics of six HIV-1 neutralizing antibodies as a function of the surface density of envelope glycoprotein gp120. Antibodies that recognize gp120 with low to moderate binding affinity displayed the most pronounced sensitivity to variation in antigen density, with qualitative and substantial quantitative changes in the energetics of the binding process as revealed by non-equilibrium and equilibrium thermodynamic analyses. In contrast, the recognition of gp120 by the antibodies with the highest affinity was considerably less influenced by variations in antigen density. These data suggest that a lower affinity of antibodies permits higher dynamics during the antigen recognition process, which may have considerable functional repercussions. These findings contribute to a better understanding of the mechanisms of antigen recognition by antibodies. They are also of importance for apprehending the impact of antigen topology on immune-defense functions of antibodies.
format article
author Maya Hadzhieva
Anastas D. Pashov
Srinivas Kaveri
Sébastien Lacroix-Desmazes
Hugo Mouquet
Jordan D. Dimitrov
author_facet Maya Hadzhieva
Anastas D. Pashov
Srinivas Kaveri
Sébastien Lacroix-Desmazes
Hugo Mouquet
Jordan D. Dimitrov
author_sort Maya Hadzhieva
title Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
title_short Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
title_full Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
title_fullStr Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
title_full_unstemmed Impact of Antigen Density on the Binding Mechanism of IgG Antibodies
title_sort impact of antigen density on the binding mechanism of igg antibodies
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/2a9f6eab595e44edb829b92bb61362e7
work_keys_str_mv AT mayahadzhieva impactofantigendensityonthebindingmechanismofiggantibodies
AT anastasdpashov impactofantigendensityonthebindingmechanismofiggantibodies
AT srinivaskaveri impactofantigendensityonthebindingmechanismofiggantibodies
AT sebastienlacroixdesmazes impactofantigendensityonthebindingmechanismofiggantibodies
AT hugomouquet impactofantigendensityonthebindingmechanismofiggantibodies
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