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Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies

A Publisher Correction to this article was published on 19 February 2019

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Abstract

Although repetitive patterns of antigens are crucial for certain immune responses, an understanding of how antibodies bind and dynamically interact with various spatial arrangements of molecules is lacking. Hence, we introduced a new method in which molecularly precise nanoscale patterns of antigens are displayed using DNA origami and immobilized in a surface plasmon resonance set-up. Using antibodies with identical antigen-binding domains, we found that all the subclasses and isotypes studied bind bivalently to two antigens separated at distances that range from 3 to 17 nm. The binding affinities of these antibodies change with the antigen distances, with a distinct preference for antigens separated by approximately 16 nm, and considerable differences in spatial tolerance exist between IgM and IgG and between low- and high-affinity antibodies.

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Fig. 1: The PSPR method.
Fig. 2: Antibody binding to precise antigen separations.
Fig. 3: Spatial tolerance is lower in low-affinity antibodies.
Fig. 4: Steady-state and dynamic analyses of multivalent patterns reveals a binding profile stratified by competing states.

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Code availability

All the code used for the computational results is available upon request.

Data availability

The raw data that support the plots within this paper and other findings of this study are provided in Supplementary Information and are available from the authors upon reasonable request.

Change history

  • 19 February 2019

    In the Supplementary Information file originally published with this Article, the Supplementary references 48–62 were missing; the amended file has now been uploaded.

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Acknowledgements

This work was funded through grants from the Swedish Research Council (grant no. 2013–5883 to B.H.), the Swedish Foundation for Strategic Research (grant FFL12–0219 to B.H.), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 724872 to B.H.) and the Knut and Alice Wallenberg foundation (Academy Fellow grant KAW2014.0241 to B.H.). The SPR instrument was funded by the SFO initiative StatRegen at Karolinska Institutet. J.T.A. was in part supported by the Research Council of Norway through its Centres of Excellence funding scheme (project no. 179573) and the Research Council of Norway (grant no. 230526/F20 and no. 274993/O70). We thank S. Foss for help with schematic antibody figures. We thank Y. Bryceson and S. Chiang for work on the experimental testing and discussions, and G. Karlsson Hedestam and A. Teixeira for discussions.

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A.S., J.T.A. and B.H. conceived the study and wrote the paper. J.T.A., I.Sa., A.G. and T.E.M. helped conceive the human antibody panel study. A.S. performed most of the experimental work on origami and SPR. I.T.H. performed most of the theoretical and modelling work. I.Sm. performed a significant proportion of the experimental work on origami and SPR. J.R. performed origami experiments and design. J.T.A., D.B., T.E.M. and A.G. performed the production and purification of the human antibody variants. All the authors contributed to writing the manuscript.

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Correspondence to Björn Högberg.

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Supplementary notes 1–4, Supplementary Figures 1–31, Supplementary Tables 1–5

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Shaw, A., Hoffecker, I.T., Smyrlaki, I. et al. Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies. Nature Nanotech 14, 184–190 (2019). https://doi.org/10.1038/s41565-018-0336-3

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