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Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image
Vibha Kumra Ahnlide1, Johannes Kumra Ahnlide1, Sebastian Wrighton1
1Division of Infection Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
Elife
|February 24, 2022
Summary
We developed SiteLoc, a novel imaging method for precise antibody binding site localization on cell surfaces. This technique overcomes limitations of current methods, enabling faster, high-throughput epitope mapping for antibody and vaccine development.
Area of Science:
- Immunology
- Biophysics
- Cell Biology
Background:
- Antibody binding to cell surface proteins is critical for immune responses.
- Epitope location significantly influences immunological outcomes.
- Current epitope identification methods are costly, slow, and not high-throughput.
Purpose of the Study:
- To develop a fast and efficient method for imaging-based molecular localization on cellular surface proteins.
- To enable accurate native antibody localization on heterogeneous cell surfaces.
- To facilitate the development of therapeutic monoclonal antibodies and vaccines.
Main Methods:
- Developed SiteLoc, an imaging-based method for molecular localization.
- Achieved nanometer-scale resolution via one-dimensional localization (distance from ligand to reference surface).
- Utilized topological image averaging to address variable cellular morphology and heterogeneous antibody binding.
Main Results:
- SiteLoc is well-suited for antibody binding site measurements on native cell surface morphology.
- Demonstrated the method's capability for accurate native antibody localization.
- Showcased applicability to other molecular distance estimations.
Conclusions:
- SiteLoc offers a significant advancement in epitope mapping and molecular localization.
- The method provides a high-throughput, cost-effective solution for antibody and vaccine development.
- SiteLoc has broad potential for various molecular distance estimation applications in biological research.

