Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.
Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (...
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doaj-f6be0b9a5a874f1cbc6558a62cdcd27c2020-11-24T21:52:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-03-01123e100545610.1371/journal.ppat.1005456Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.Alison E MahanMadeleine F JenneweinTodd SuscovichKendall DionneJacquelynne TedescoAmy W ChungHendrik StreeckMaria PauHanneke SchuitemakerDon FrancisPatricia FastDagna LauferBruce D WalkerLindsey BadenDan H BarouchGalit AlterAntibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo. .http://europepmc.org/articles/PMC4794126?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alison E Mahan Madeleine F Jennewein Todd Suscovich Kendall Dionne Jacquelynne Tedesco Amy W Chung Hendrik Streeck Maria Pau Hanneke Schuitemaker Don Francis Patricia Fast Dagna Laufer Bruce D Walker Lindsey Baden Dan H Barouch Galit Alter |
spellingShingle |
Alison E Mahan Madeleine F Jennewein Todd Suscovich Kendall Dionne Jacquelynne Tedesco Amy W Chung Hendrik Streeck Maria Pau Hanneke Schuitemaker Don Francis Patricia Fast Dagna Laufer Bruce D Walker Lindsey Baden Dan H Barouch Galit Alter Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. PLoS Pathogens |
author_facet |
Alison E Mahan Madeleine F Jennewein Todd Suscovich Kendall Dionne Jacquelynne Tedesco Amy W Chung Hendrik Streeck Maria Pau Hanneke Schuitemaker Don Francis Patricia Fast Dagna Laufer Bruce D Walker Lindsey Baden Dan H Barouch Galit Alter |
author_sort |
Alison E Mahan |
title |
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. |
title_short |
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. |
title_full |
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. |
title_fullStr |
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. |
title_full_unstemmed |
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. |
title_sort |
antigen-specific antibody glycosylation is regulated via vaccination. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2016-03-01 |
description |
Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo. . |
url |
http://europepmc.org/articles/PMC4794126?pdf=render |
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