CV Science

Yannick HAMON PhD in immunology

Course and current status

Current : INSERM staff scientist @ CIML (Centre d'Immunology de Marseille Luminy)

Team Hai-Tao HE & Didier Marguet

Scientific summary

T cell antigen recognition is a key element of the adpative immunity initiatiated by the binding of the T-cell receptor (TCR) to antigenic peptides presented by MHC molecules. This consequently activates signalling cascades inside T-cells leading to differentiation into effector and memory T cells. While the main key players involved in the TCR signalling pathway have been identified so far, the precise molecular mechanism underlying this activation remains poorly understood. in this context membrane rafts have been proposed to be involved into the TCR-mediated signal transduction. However due to methodological limitations, the biologocal significance or even the very existence of rafts have remained elusive. measuring lateral diffusion of molecules at different spatial scales by spot variation fluorescence correlation spectroscopy enabled us to identify nano-sized raft domains in live cell membranesand to examine their implications in cell signaling. We show that the TCR/CD3 complex exhibits dynamic partitioning into sphingolipid/cholesterol-dependent raft nanodomains with a time-scale of milliseconds. By accurately controlling raft formation, we further show that raft nanodomains paly an essential role in initiation of TCR signal transduction. Specially we found that following antigen recognition, TCR dependant intracellular calcium mobilization is strongly impaired upon nanodomains impediment using a newly developed approach named "Methods for Automated and Accurate Analysis of Cell signals" (MAAACS). Our studi throws new light on the importance of the membrane lateral organization and dynamics in the initiation of TCR signaling pathways upon antigenic challenge.