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Membrane-anchored DNA nanojunctions enable closer antigen-presenting cell–T-cell contact in elevated T-cell receptor triggering

Nature Nanotechnology volume 18, pages 818–827 (2023)Cite this article

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An Author Correction to this article was published on 19 September 2023

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Abstract

How the engagement of a T-cell receptor to antigenic peptide-loaded major histocompatibility complex on antigen-presenting cells (APCs) initiates intracellular signalling cascades in T cells is not well understood. In particular, the dimension of the cellular contact zone is regarded as a determinant, but its influence remains controversial. This is due to the need for appropriate strategies for manipulating intermembrane spacing between the APC–T-cell interfaces without involving protein modification. Here we describe a membrane-anchored DNA nanojunction with distinct sizes to extend, maintain and shorten the APC–T-cell interface down to 10 nm. Our results suggest that the axial distance of the contact zone is critical in T-cell activation, presumably by modulating protein reorganization and mechanical force. Notably, we observe the promotion of T-cell signalling by shortening the intermembrane distance.

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Fig. 1: Construction and characterization of TDNs for cell-surface engineering.
Fig. 2: Building DNJs for manipulation of intermembrane spacing.
Fig. 3: Influence of high-density DNJs on the activation of T cells.
Fig. 4: Modulating T-cell activation with DNJ-mediated intermembrane distance.
Fig. 5: Studying the molecular mechanism of TCR signalling.

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Data availability

The data supporting the findings of this study are available within the article and its Supplementary Information. Source data are provided with this paper and available via Zenodo at https://doi.org/10.5281/zenodo.7424802.

Code availability

The code designed for data collection and analysis of this study is available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank X. Yu and Q. Zou at Shanghai Jiao Tong University School of Medicine for providing technical assistance. This work is supported by the National Key Research Program (2021YFA0910100 (to L.Q.), 2018YFC1602900 (to L.Q.) and 2019YFA0905800 (to W.T.)), the National Natural Science Foundation of China (NSFC 21922404 (to L.Q.), 22174039 (to L.Q.), 22107027 (to Y.L.) and 21827811 (to W.T.)), the Science and Technology Project of Hunan Province (2021RC4022 (to L.Q.), 2019SK2201 (to W.T.), 2018RS3035 (to L.Q.) and 2017XK2103 (to W.T.)) and Shenzhen excellent science and technology innovation talents training project (RCBS20200714114821377 (to Y.L.)).

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  1. These authors contributed equally: Yulin Du, Yifan Lyu.

Authors and Affiliations

  1. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, China

    Yulin Du, Yifan Lyu, Jie Lin, Chunran Ma, Qiang Zhang, Yutong Zhang, Liping Qiu & Weihong Tan

  2. The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China

    Liping Qiu & Weihong Tan

  3. Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Weihong Tan

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Contributions

Y.D. and L.Q. conceived and designed the research. Y.D., Y.L., J.L., C.M., Q.Z. and Y.Z. conducted the experiments. Y.D. performed the analysis. Y.D. and Y.L. performed the imaging analysis and reconstruction of cell membrane morphology. Y.D., L.Q. and W.T. drafted and revised the manuscript. All the authors commented on the paper.

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Correspondence to Liping Qiu or Weihong Tan.

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Nature Nanotechnology thanks Michael Dustin, Wolfgang Schamel and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Du, Y., Lyu, Y., Lin, J. et al. Membrane-anchored DNA nanojunctions enable closer antigen-presenting cell–T-cell contact in elevated T-cell receptor triggering. Nat. Nanotechnol. 18, 818–827 (2023). https://doi.org/10.1038/s41565-023-01333-2

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