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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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.
The code designed for data collection and analysis of this study is available from the corresponding authors upon reasonable request.
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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.)).
The authors declare no competing interests.
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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. (2023). https://doi.org/10.1038/s41565-023-01333-2
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