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The spatial and temporal organization of T cell signaling molecules is increasingly accepted as a crucial step in controlling T cell activation. CD222, also known as the cation-independent mannose 6-phosphate/insulin-like growth factor 2 receptor, is the central component of endosomal transport pathways. In this study, we show that CD222 is a key regulator of the early T cell signaling cascade. Knockdown of CD222 hampers the effective progression of TCR-induced signaling and subsequent effector functions, which can be rescued via reconstitution of CD222 expression. We decipher that Lck is retained in the cytosol of CD222-deficient cells, which obstructs the recruitment of Lck to CD45 at the cell surface, resulting in an abundant inhibitory phosphorylation signature on Lck at the steady state. Hence, CD222 specifically controls the balance between active and inactive Lck in resting T cells, which guarantees operative T cell effector functions.

Original publication

DOI

10.4049/jimmunol.1303349

Type

Journal article

Journal

J Immunol

Publication Date

15/09/2014

Volume

193

Pages

2718 - 2732

Keywords

Animals, Cell Line, Tumor, Humans, Jurkat Cells, Leukocyte Common Antigens, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Membrane Transport Proteins, Mice, Phosphorylation, RNA Interference, RNA, Small Interfering, Receptor, IGF Type 2, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes