AIRR-C Seminar Series, April 25th, 2024 - Marta T. Borowska, Stanford University, US
20.8 هزار بار بازدید -
ماه قبل
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Biochemical and biophysical characterization of
Biochemical and biophysical characterization of natural polyreactivity in antibodies
Early Career Speaker: Marta T. Borowska, Stanford University
Talk abstract
To become specialized binders, antibodies undergo a process called affinity maturation to maximize their binding affinity. Despite this process, some antibodies retain low-affinity binding to diverse epitopes in a phenomenon called polyreactivity. Here we seek to understand the molecular basis of this polyreactivity in antibodies. Our results highlight that polyreactive antigen-binding fragments (Fabs) bind their targets with low affinities, comparable to T cell receptor recognition of autologous classical major histocompatibility complex. Extensive mutagenic studies find no singular amino acid residue or biochemical property responsible for polyreactive interaction, suggesting that polyreactive antibodies use multiple strategies for engagement. Finally, our crystal structures and all-atom molecular dynamics simulations of polyreactive Fabs show increased rigidity compared to their monoreactive relatives, forming a neutral and accessible platform for diverse antigens to bind. Together, these data support a cooperative strategy of rigid neutrality in establishing the polyreactive status of an antibody molecule.
Speaker bio
Marta grew up in Łódź and studied in Poland and Austria before moving to the University of Chicago on a year-long fellowship to complete her master’s studies. She then joined the University of Chicago as a Ph.D. candidate to pair her interests in structural biology and immunology. She naturally gravitated to the area of unconventional immune recognition because its mechanisms are largely unknown. Now, she continues to use this foundation as a springboard for engineering designer approaches in immunotherapy at Stanford University. Her long-term goal is to be an independent investigator running a research laboratory at an academic institute. Marta is broadly interested in complex immune signaling and aims to develop protein engineering approaches to control and modulate it. She enjoys playing chess and exploring science through art and is a proud member of the LBGTQ+ community.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
Early Career Speaker: Marta T. Borowska, Stanford University
Talk abstract
To become specialized binders, antibodies undergo a process called affinity maturation to maximize their binding affinity. Despite this process, some antibodies retain low-affinity binding to diverse epitopes in a phenomenon called polyreactivity. Here we seek to understand the molecular basis of this polyreactivity in antibodies. Our results highlight that polyreactive antigen-binding fragments (Fabs) bind their targets with low affinities, comparable to T cell receptor recognition of autologous classical major histocompatibility complex. Extensive mutagenic studies find no singular amino acid residue or biochemical property responsible for polyreactive interaction, suggesting that polyreactive antibodies use multiple strategies for engagement. Finally, our crystal structures and all-atom molecular dynamics simulations of polyreactive Fabs show increased rigidity compared to their monoreactive relatives, forming a neutral and accessible platform for diverse antigens to bind. Together, these data support a cooperative strategy of rigid neutrality in establishing the polyreactive status of an antibody molecule.
Speaker bio
Marta grew up in Łódź and studied in Poland and Austria before moving to the University of Chicago on a year-long fellowship to complete her master’s studies. She then joined the University of Chicago as a Ph.D. candidate to pair her interests in structural biology and immunology. She naturally gravitated to the area of unconventional immune recognition because its mechanisms are largely unknown. Now, she continues to use this foundation as a springboard for engineering designer approaches in immunotherapy at Stanford University. Her long-term goal is to be an independent investigator running a research laboratory at an academic institute. Marta is broadly interested in complex immune signaling and aims to develop protein engineering approaches to control and modulate it. She enjoys playing chess and exploring science through art and is a proud member of the LBGTQ+ community.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
ماه قبل
در تاریخ 1403/03/21 منتشر شده
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