Longitudinal proteomic analysis of T cell differentiation in vivo reveals dynamic changes of the interactome

T cell differentiation has been extensively studied on the cellular, transcriptional, and epigenetic levels. However, proteomic profiling of T cell differentiation directly ex-vivo has not been performed, despite numerous studies demonstrating discrepancy between transcriptional and proteomic profiles of cells. Here, we present the first exhaustive longitudinal proteomic profiling of T cell differentiation in vivo using the well-characterized lymphocytic choriomeningitis virus (LCMV) mouse model. We performed ex-vivo protein abundance profiling of effector to memory differentiation (TEFF/TMEM) and early to late exhausted T cell (Tex) differentiation following LCMV infection with the acute Armstrong and chronic Clone-13 strains, respectively. Our results show dynamic alterations of the T cell proteome during differentiation that are either common or distinct for acute and chronic infection. Importantly, several proteins that are significantly abundant for a specific cell state were not previously highlighted by transcriptional profiling. Thus, our study provides a comprehensive resource for the proteome of in vivo T cell differentiation that could unravel novel protein interactions with potential therapeutic implications. ### Competing Interest Statement The authors have declared no competing interest.