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Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization

Abstract : We investigate adhesion and molecular organization of the plasma membrane of T lymphocytes interacting with a surrogate antigen presenting cell comprising glass supported ordered arrays of antibody (α-CD3) nano-dots dispersed in a non-adhesive matrix of polyethylene glycol (PEG). The local membrane adhesion and topography, as well as the distribution of the T cell receptors (TCRs) and the kinase ZAP-70, is influenced by dot-geometry, whereas cell spreading area is determined by the overall average density of the ligands rather than specific characteristics of the dots. TCR clusters are recruited preferentially to the nano-dots and the TCR cluster size distribution has a weak dot-size dependence. On the patterns, the clusters are larger, more numerous, and more enriched in TCR, as compared to the homogeneously distributed ligands at comparable concentrations. These observations support the idea that non-ligated TCR residing in the non-adhered parts of the proximal membrane are able to diffuse and enrich the existing clusters at the ligand dots. However, long distance transport is impaired and cluster centralization in form of a central Supramolecular cluster (cSMAC) is not observed. Time-lapse imaging of early cell-surface contacts indicates that the ZAP-70 microclusters are directly recruited to the site of the antibody dots and this process is concomitant with membrane adhesion. These results together point to a complex interplay of adhesion, molecular organization and activation in response to spatially modulated stimulation.
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https://hal-amu.archives-ouvertes.fr/hal-01780328
Contributor : Kheya Sengupta <>
Submitted on : Friday, May 4, 2018 - 10:48:17 AM
Last modification on : Wednesday, August 19, 2020 - 12:08:15 PM
Long-term archiving on: : Tuesday, September 25, 2018 - 7:09:47 AM

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Pierre Dillard, Fuwei Pi, Annemarie Lellouch, Laurent Limozin, Kheya Sengupta. Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization. Integrative biology, Royal Society of Chemistry, 2016, 8 (3), pp.287 - 301. ⟨10.1039/C5IB00293A⟩. ⟨hal-01780328⟩

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