Regulation of T cell receptor signaling by activation-induced zinc influx

Mingcan Yu, Won Woo Lee, Deepak Tomar, Sergey Pryshchep, Marta Czesnikiewicz-Guzik, David L. Lamar, Guangjin Li, Karnail Singh, Lu Tian, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Zinc is a trace element that is essential for innate and adaptive immune responses. In addition to being a structural element of many proteins, zinc also functions as a neurotransmitter and an intracellular messenger. Temporal or spatial changes in bioavailable zinc may influence the activity of several enzymes, including kinases and phosphatases. We provide evidence that zinc functions as an ionic signaling molecule after T cell activation. Cytoplasmic zinc concentrations increased within 1 min after T cell receptor (TCR) triggering, in particular in the subsynaptic compartment. The increase depended on the extracellular zinc concentrations and was inhibited by silencing zinc transporter Zip6. Increased zinc influx reduced the recruitment of SHP-1 to the TCR activation complex, augmented ZAP70 phosphorylation and sustained calcium influx. By calibrating TCR activation thresholds, increased extracellular zinc bioavailability facilitated the induction of T cell proliferative responses to suboptimal stimuli.

Original languageEnglish (US)
Pages (from-to)775-785
Number of pages11
JournalJournal of Experimental Medicine
Volume208
Issue number4
DOIs
StatePublished - Apr 11 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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