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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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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T-Cell Antigen Receptor
Tail
Phospholipids
T-Lymphocytes
T-Cell Antigen Receptor-CD3 Complex
Immunological Synapses
CD3 Antigens
Proline
Transgenic Mice
Cell Biology
Lipids
Peptides
Mutation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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The cytoplasmic tail of the T cell receptor CD3 ε subunit contains a phospholipid-binding motif that regulates T cell functions. / DeFord-Watts, Laura M.; Tassin, Tara C.; Becker, Amy M.; Medeiros, Jennifer J.; Albanesi, Joseph P.; Love, Paul E.; Wülfing, Christoph; Van Oers, Nicolai S C.

In: Journal of Immunology, Vol. 183, No. 2, 15.07.2009, p. 1055-1064.

Research output: Contribution to journalArticle

DeFord-Watts, Laura M. ; Tassin, Tara C. ; Becker, Amy M. ; Medeiros, Jennifer J. ; Albanesi, Joseph P. ; Love, Paul E. ; Wülfing, Christoph ; Van Oers, Nicolai S C. / The cytoplasmic tail of the T cell receptor CD3 ε subunit contains a phospholipid-binding motif that regulates T cell functions. In: Journal of Immunology. 2009 ; Vol. 183, No. 2. pp. 1055-1064.
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