The cytoplasmic tail of the T cell receptor CD3 ε subunit contains a phospholipid-binding motif that regulates T cell functions

Laura M. DeFord-Watts, Tara C. Tassin, Amy M. Becker, Jennifer J. Medeiros, Joseph P. Albanesi, Paul E. Love, Christoph Wülfing, Nicolai S C Van Oers

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52 Scopus citations

Abstract

The CD3 ε subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 ε, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 ε to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and PI(4,5)P2. Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 ε localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 ε lipid-binding domain in T cell biology.

Original languageEnglish (US)
Pages (from-to)1055-1064
Number of pages10
JournalJournal of Immunology
Volume183
Issue number2
DOIs
StatePublished - Jul 15 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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