Dissection of immune cell signaling by mass spectrometry

Romain Roncagalli

With the recent success of immunotherapies, understanding signal transduction re-emerges as a major interest for manipulating T cells. Although extensive knowledge has been accumulated over decades on molecular key players and biological processes involved in the TCR signaling pathway, an integrated resource deciphering the earliest molecular events is still missing in primary T cells. As a consequence the design of new treatments is often hazardous. Using different approaches combining Mass spectrometry analysis and genetic engineering, we identified and monitored the dynamic and stoichiometry of hundreds of molecular events regulated by the TCR stimulation in primary mouse T cells.  Additionally, we developed computational analysis exploiting correlations between protein associations for predicting inferences between them. This methodology unveiled signaling marks providing insights about the engaged cellular programs. These results lay the foundation for an integrated and comprehensive understanding of the molecular mechanisms that regulate T cell functions, a prerequisite for designing and generating drugs for medical treatments.