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

Authors
  • Pfisterer, Karin
  • Forster, Florian
  • Paster, Wolfgang
  • Supper, Verena
  • Ohradanova-Repic, Anna
  • Eckerstorfer, Paul
  • Zwirzitz, Alexander
  • Donner, Clemens
  • Boulegue, Cyril
  • Schiller, Herbert B
  • Ondrovičová, Gabriela
  • Acuto, Oreste
  • Stockinger, Hannes
  • Leksa, Vladimir
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Sep 15, 2014
Volume
193
Issue
6
Pages
2718–2732
Identifiers
DOI: 10.4049/jimmunol.1303349
PMID: 25127865
Source
Medline
License
Unknown

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.

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