Modulation of B cell receptor activation by antibody competition
Yuanyuan He1,2, Zijian Guo1,2, Michael D Vahey1,2
1Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
Biorxiv : the Preprint Server for Biology
|November 28, 2024
Summary
Pre-existing antibodies can mask viral epitopes, hindering B cell recognition. Antibody properties like affinity and epitope proximity determine masking potency, offering insights for improved immunogen design.
Area of Science:
- Immunology
- Virology
- Structural Biology
Background:
- Pre-existing antibodies can interfere with new B cell responses during viral infections.
- The mechanisms and factors governing antibody-mediated epitope masking are not fully understood.
- Understanding epitope accessibility is crucial for effective vaccine and therapeutic antibody design.
Purpose of the Study:
- To investigate how antibodies influence the accessibility of viral epitopes for B cell recognition.
- To identify factors that determine the effectiveness of epitope masking by competing antibodies.
- To explore the potential for antibodies to either inhibit or enhance epitope accessibility.
Main Methods:
- Utilized engineered, influenza-virus-reactive B cells to model B cell-epitope interactions.
- Analyzed the impact of antibody properties (affinity, kinetics, valency) on epitope masking.
- Assessed epitope accessibility on influenza hemagglutinin using various antibody competition assays.
Main Results:
- Membrane-proximal epitopes on influenza hemagglutinin are less accessible due to direct and indirect antibody competition.
- The potency of epitope masking is influenced by epitope location, antibody affinity, kinetics, and valency.
- Identified a specific antibody that enhances the accessibility of previously hidden viral epitopes, contrary to typical inhibitory effects.
Conclusions:
- Established key principles governing antibody-mediated epitope masking on viral surfaces.
- Demonstrated that epitope masking is a complex interplay of antibody characteristics and epitope properties.
- Findings provide a framework for designing immunogens that elicit protective B cell responses against conserved viral epitopes.
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