Alexander Zwirzitz

Anna Ohradanova-Repic

Clemens Donner

Cyril Boulegue

Florian Forster

Gabriela Ondrovičová

Hannes Stockinger

Herbert B. Schiller

Karin Pfisterer

Kiess

Magee

Oreste Acuto

Paul Eckerstorfer

Rossy

Sander

Verena Supper

Vladimir Leksa

Wolfgang Paster

Yurchak

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.</jats:p

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The Journal of Immunology

The Late Endosomal Transporter CD222 Directs the Spatial Distribution and Activity of Lck

The Late Endosomal Transporter CD222 Directs the Spatial Distribution and Activity of Lck

Abstract

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