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Updated: Jan 28, 2026
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Determining Binding Affinity KD of Radiolabeled Antibodies to Immobilized Antigens
Published on: June 23, 2022
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Antigen binding triggers long-range conformational changes in monoclonal antibodies
Davide Bianchi1, Simona Saporiti2, Wolf Palinsky3
1Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Frontiers in Immunology
|January 26, 2026
Summary
Antigen binding to therapeutic monoclonal antibodies (mAbs) alters their structure, enhancing immune receptor interactions. This structural reshaping, influenced by glycosylation, is key for optimizing antibody therapies.
Area of Science:
- Biochemistry
- Immunology
- Computational Biology
Background:
- Monoclonal antibodies (mAbs) traditionally bind antigens for target recognition.
- Emerging evidence indicates antigen binding modulates mAb conformation and effector functions.
- Understanding antigen engagement's impact on antibody structure and immune receptor interaction is crucial for therapy optimization.
Purpose of the Study:
- Investigate how antigen engagement alters the structural organization of therapeutic IgG1 antibodies.
- Determine the influence of antigen binding on the interaction of therapeutic antibodies with FcγRIIIa.
Main Methods:
- Utilized accelerated molecular dynamics simulations.
- Analyzed two therapeutic mAbs (adalimumab and avelumab) in various glycosylation states.
- Focused on structural and dynamic consequences of antigen binding.
Main Results:
- Identified long-range dynamic correlations between antigen-binding regions and Fc domains, indicating allosteric communication.
- Antigen engagement increases exposure of Fc residues vital for immune receptor recognition.
- Glycosylation and light chain isotype modulate these antigen-binding effects.
Conclusions:
- Antigen engagement triggers coordinated motions that reshape mAb architecture.
- This reshaping regulates interactions with immune receptors.
- Findings offer insights for designing functionally optimized therapeutic antibodies.
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