NIH VideoCast - The multi-faceted role of the IgG glycan

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The multi-faceted role of the IgG glycan

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Air date:	Wednesday, January 18, 2017, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 443 (72 Live, 371 On-demand)
Category:	Immunology
Runtime:	01:09:38
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group Seminar Series Beyond their role in pathogen neutralization, antibodies mediate pathogen control and clearance via the recruitment of innate immune effector functions including phagocytosis and cytotoxicity but also via the homeostatic regulation of the immune activation. Two modifications to the constant domain of the IgG antibody control this biological activity: 1) the irreversible genomic selection of isotype/subclass and 2) a more subtle alteration in Fc-glycosylation, that together provide instructions to the innate immune system . Because glycosylation alters the affinity of antibodies for Fc-receptors on innate immune cells, mounting evidence suggests that glycosylation may be actively exploited by the immune system to tune antibody biological activity far beyond pathogen control and clearance. While many monoclonal therapeutics have exploited glycosylation, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors is unknown. Two distinct functional roles of antibodies will be discussed in this presentation including the role of antibodies the regulation of the induction of the fhumoral immune response as well as in the regulation of antibody transfer from mother to child. Galit Alter received her PhD in experimental medicine from McGill University, and is currently an Associate Professor in Medicine at Harvard Medical School. Over the past 8 years her research has focused on understanding the role of the innate immune response to chronic viral infections, including HIV and HCV, with a focus on defining the role of Natural Killer (NK) cells in antiviral control. Recently, these studies have shifted gears to begin to define the mechanism by which these innate immune effector cells may be harnessed through vaccination to gain more effective control over viral replication. To do this, her current research interests lie in defining the role of innate immune recruiting antibodies in providing protection from infection. Specifically, she is working towards defining the pathways that result in the targeted production of “protective” antibody glycans to enhance the production of antibodies that can potently block infections. Advancement in understanding how to manipulate the antibody glycan in a targeted manner through vaccination will also lead to the generation of vaccines with broader applications by extending to the improvement of therapeutic vaccines for the treatment of malignancies and autoimmune diseases as well. This knowledge will provide insights into natural antibody glycovariation, and lead to the development of novel approaches to strategically tailor vaccines to induce innate immune cell-recruiting antibodies, with the hope that these findings will ultimately revolutionize the application of vaccines to treat and prevent a remarkably larger range of diseases.

NLM Title:	The multi-faceted role of the IgG glycan / Galit Alter.
Author:	Alter, Galit. National Institutes of Health (U.S.). Immunology Interest Group,
Publisher:
Abstract:	(CIT): Immunology Interest Group Seminar Series Beyond their role in pathogen neutralization, antibodies mediate pathogen control and clearance via the recruitment of innate immune effector functions including phagocytosis and cytotoxicity but also via the homeostatic regulation of the immune activation. Two modifications to the constant domain of the IgG antibody control this biological activity: 1) the irreversible genomic selection of isotype/subclass and 2) a more subtle alteration in Fc-glycosylation, that together provide instructions to the innate immune system . Because glycosylation alters the affinity of antibodies for Fc-receptors on innate immune cells, mounting evidence suggests that glycosylation may be actively exploited by the immune system to tune antibody biological activity far beyond pathogen control and clearance. While many monoclonal therapeutics have exploited glycosylation, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors is unknown. Two distinct functional roles of antibodies will be discussed in this presentation including the role of antibodies the regulation of the induction of the fhumoral immune response as well as in the regulation of antibody transfer from mother to child. Galit Alter received her PhD in experimental medicine from McGill University, and is currently an Associate Professor in Medicine at Harvard Medical School. Over the past 8 years her research has focused on understanding the role of the innate immune response to chronic viral infections, including HIV and HCV, with a focus on defining the role of Natural Killer (NK) cells in antiviral control. Recently, these studies have shifted gears to begin to define the mechanism by which these innate immune effector cells may be harnessed through vaccination to gain more effective control over viral replication. To do this, her current research interests lie in defining the role of innate immune recruiting antibodies in providing protection from infection. Specifically, she is working towards defining the pathways that result in the targeted production of "protective" antibody glycans to enhance the production of antibodies that can potently block infections. Advancement in understanding how to manipulate the antibody glycan in a targeted manner through vaccination will also lead to the generation of vaccines with broader applications by extending to the improvement of therapeutic vaccines for the treatment of malignancies and autoimmune diseases as well. This knowledge will provide insights into natural antibody glycovariation, and lead to the development of novel approaches to strategically tailor vaccines to induce innate immune cell-recruiting antibodies, with the hope that these findings will ultimately revolutionize the application of vaccines to treat and prevent a remarkably larger range of diseases.
Subjects:	Antibodies, Neutralizing--immunology Antibodies, Viral--immunology Glycosylation Immunoglobulin Fc Fragments--immunology Immunoglobulin G--immunology Polysaccharides--immunology
Publication Types:	Lecture Webcast

NLM Classification:	QW 601
NLM ID:	101700295
CIT Live ID:	18544
Permanent link:	https://videocast.nih.gov/watch=18544

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