What is it about?
B cell receptor (BCR)–antigen interactions in vivo take place in a two-dimensional (2D) environment, while in vitro antibody-antigen interactions occur in three-dimensional (3D) conditions. The rotational alignments of antigen and BCR or antibody play a critical role in the kinetic rates of the binding reaction. However, the impact of these rotations in 2D vs. 3D conditions is currently unknown. This study uses theory and empirical data to model and estimate the global rotational rates of BCR and antibody reactive sites and the effective kinetic rates in both 2D and 3D conditions.
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Why is it important?
Our framework helps compute unavailable 2D BCR-antigen binding rates from existing 3D data. It reveals the limits above which available empirical 3D antibody-antigen kinetic binding rates are wrong estimates of actual 2D BCR-antigen rates.
Perspectives
It has been challenging and inspiring to discover how experiments might not be the ground truth without a proper theoretical background as it is often presupposed. While this is well accepted in other areas, we hope this paves the ground for synergistic collaborations between experimentalists and mathematical modelers in B-cell Immunology.
Jose Faro
Read the Original
This page is a summary of: B cell receptors and free antibodies have different antigen-binding kinetics, Proceedings of the National Academy of Sciences, August 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2220669120.
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