Interleukin-2 shapes the cytotoxic T cell proteome and immune-environment sensing

ABSTRACT: Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to control the differentiation of effector CD8+ cytotoxic T cells (CTL). Using high-resolution mass spectrometry, we have generated an in-depth characterisation of how IL-2 and JAKs configure the CTL proteome to control CTL function. We found that IL-2-JAK1/3 signaling selectively regulated the abundance of a key subset of proteins influencing the accumulation of critical cytokines and effector molecules in T cells. Moreover, IL-2 controlled the concentration of proteins that support core metabolic processes essential for cellular fitness. One fundamental insight was the dominant role for IL-2 in controlling how effector T cells respond to their microenvironment. IL-2-JAK1/3 signaling pathways thus controlled the abundance of nutrient transporters, nutrient sensors and critical oxygen sensing molecules. The data provide key insights of how IL-2 controls T cell function and highlight signaling mechanisms and transcription factors that link oxygen sensing to transcriptional control of CD8+ T cell differentiation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cd8-positive, Primary Cell, T Cell, Cytotoxic T Cell

SUBMITTER: Sarah Ross  

LAB HEAD: Doreen Ann Cantrell

PROVIDER: PXD008112 | Pride | 2018-04-17

REPOSITORIES: Pride