Molecular-scale spatio-chemical control of the activating-inhibitory signal integration in NK cells

Toledo E, Le Saux G, Edri A, Li L, Rosenberg M, Keidar Y, Bhingardive V, Radinsky O, Hadad U, Di Primo C, Buffeteau T, Smith AS, Porgador A, Schvartzman M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 7

Article Number: eabc1640

Journal Issue: 24

DOI: 10.1126/sciadv.abc1640

Abstract

The role of juxtaposition of activating and inhibitory receptors in signal inhibition of cytotoxic lymphocytes remains strongly debated. The challenge lies in the lack of tools that allow simultaneous spatial manipulation of signaling molecules. To circumvent this, we produced a nanoengineered multifunctional platform with molecular-scale spatial control of ligands, which was applied to elucidate KIR2DL1-mediated inhibition of NKG2D signaling - receptors of natural killer cells. This platform was conceived by bimetallic nanodot patterning with molecular-scale registry, followed by a ternary functionalization with distinct moieties. We found that a 40-nm gap between activating and inhibitory ligands provided optimal inhibitory conditions. Supported by theoretical modeling, we interpret these findings as a consequence of the size mismatch and conformational flexibility of ligands in their spatial interaction. This highly versatile approach provides an important insight into the spatial mechanism of inhibitory immune checkpoints, which is essential for the rational design of future immunotherapies.

Authors with CRIS profile

Long Li Physics Underlying Life Science (PULS) Ana-Suncana Smith Physics Underlying Life Science (PULS)

Involved external institutions

Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב IL Israel (IL) Université de Bordeaux FR France (FR)

How to cite

APA:

Toledo, E., Le Saux, G., Edri, A., Li, L., Rosenberg, M., Keidar, Y.,... Schvartzman, M. (2021). Molecular-scale spatio-chemical control of the activating-inhibitory signal integration in NK cells. Science Advances, 7(24). https://doi.org/10.1126/sciadv.abc1640

MLA:

Toledo, Esti, et al. "Molecular-scale spatio-chemical control of the activating-inhibitory signal integration in NK cells." Science Advances 7.24 (2021).

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