The late endosomal transporter CD222 directs the spatial distribution and activity of Lck

K. Pfisterer, F. Forster, W. Paster, V. Supper, A. Ohradanova-Repic, P. Eckerstorfer, A. Zwirzitz, C. Donner, C. Boulegue, H.B. Schiller, G. Ondrovičová, O. Acuto, H. Stockinger, V. Leksa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)2718-2732
Number of pages15
JournalJournal of Immunology
Volume193
Issue number6
DOIs
Publication statusPublished - 15 Sept 2014

Fingerprint

Dive into the research topics of 'The late endosomal transporter CD222 directs the spatial distribution and activity of Lck'. Together they form a unique fingerprint.

Cite this