Details

Autor(en) / Beteiligte

• Lacouture, Claire
• Chaves, Beatriz
• Guipouy, Delphine
• Houmadi, Raïssa
• Duplan-Eche, Valérie
• Allart, Sophie
• Destainville, Nicolas
• Dupré, Loïc

Titel

LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity

Ist Teil von

• Nature communications, 2024-01, Vol.15 (1), p.407-407, Article 407

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• T-cell cytotoxic function relies on the cooperation between the highly specific but poorly adhesive T-cell receptor (TCR) and the integrin LFA-1. How LFA-1-mediated adhesion may scale with TCR stimulation strength is ill-defined. Here, we show that LFA-1 conformation activation scales with TCR stimulation to calibrate human T-cell cytotoxicity. Super-resolution microscopy analysis reveals that >1000 LFA-1 nanoclusters provide a discretized platform at the immunological synapse to translate TCR engagement and density of the LFA-1 ligand ICAM-1 into graded adhesion. Indeed, the number of high-affinity conformation LFA-1 nanoclusters increases as a function of TCR triggering strength. Blockade of LFA-1 conformational activation impairs adhesion to target cells and killing. However, it occurs at a lower TCR stimulation threshold than lytic granule exocytosis implying that it licenses, rather than directly controls, the killing decision. We conclude that the organization of LFA-1 into nanoclusters provides a calibrated system to adjust T-cell killing to the antigen stimulation strength.