Laboratoire de Physique Théorique
Toulouse - UMR 5152

In the context of a PhD thesis co-supervised by a biologist from Infinity and a theoretical physicist from LPT, the role played by nanoclusters of LFA-1, an integrin found in white blood cells, was investigated. LFA-1 can be found in two main configurations, active and inactive. The activation of LFA-1 is a key step of the immune response of cytotoxic T lymphocytes, when they come into contact with infected or cancer cells. The active form enables the anchoring of the lymphocyte to the target cell in order to kill it. This work deciphers the graded response on the T lymphocytes in function of the antigenic stimulation strength, eventually leading to the death of the target cell above a given threshold. This collaboration uses the experimental approaches of Immunology, as well as the tools of Statistical Physics to rationalize the experimental observations. Notably, LFA-1 is found to be organized in submicrometric clusters, that can only be observed with the help of superresolution fluorescence microscopy. The nanoclusters act as all-or-nothing conformation switches ensuring the cooperative behavior in integrin binding to the target cell. The organization of LFA-1 into nanoclusters provides a calibrated system to adjust T lymphocyte killing to the antigen stimulation strength.

C. Lacouture et al., LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity, Nat. Commun. 15, 407 (2024)

Contact :Claire Lacouture, Nicolas Destainville