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Nat Nanotechnol. 2018 Jul;13(7):610-617. doi: 10.1038/s41565-018-0113-3. Epub 2018 Apr 30.

Full control of ligand positioning reveals spatial thresholds for T cell receptor triggering.

Author information

1
Department of Mechanical Engineering, Columbia University, New York, NY, USA.
2
Center for Nanoscale Materials, Argonne National Laboratory, Argonne, IL, USA.
3
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.
4
The Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
5
Mechanobiology Institute of Singapore, National University of Singapore, Singapore, Singapore.
6
Department of Biological Sciences, Columbia University, New York, NY, USA.
7
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA. michael.dustin@kennedy.ox.ac.uk.
8
The Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. michael.dustin@kennedy.ox.ac.uk.
9
Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY, USA. sw2128@columbia.edu.

Abstract

Elucidating the rules for receptor triggering in cell-cell and cell-matrix contacts requires precise control of ligand positioning in three dimensions. Here, we use the T cell receptor (TCR) as a model and subject T cells to different geometric arrangements of ligands, using a nanofabricated single-molecule array platform. This comprises monovalent TCR ligands anchored to lithographically patterned nanoparticle clusters surrounded by mobile adhesion molecules on a supported lipid bilayer. The TCR ligand could be co-planar with the supported lipid bilayer (2D), excluding the CD45 transmembrane tyrosine phosphatase, or elevated by 10 nm on solid nanopedestals (3D), allowing closer access of CD45 to engaged TCR. The two configurations resulted in different T cell responses, depending on the lateral spacing between the ligands. These results identify the important contributions of lateral and axial components of ligand positioning and create a more complete foundation for receptor engineering for immunotherapy.

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