Regulation of TCR signal transduction in murine thymocytes by multiple TCR ζ-chain signaling motifs

Nicolai S C Van Oers, Paul E. Love, Elizabeth W. Shores, Arthur Weiss

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

The αβ TCR is a multimeric protein complex comprising ligand-binding and signal-transducing subunits. The signal transduction processes are mediated by the immunoreceptor tyrosine-based activation motifs (ITAMs), and up to 10 ITAMs are present within a single TCR complex. This multiplicity may allow for signal amplification and/or the formation of qualitatively distinct intracellular signals. Notably, the TCR-ζ subunit contains three ITAMs, and exists as a disulfide-linked homodimer in the TCR complex. In normal murine thymocytes and peripheral T cells, a proportion of TCR-ζ molecules is constitutively tyrosine phosphorylated and associated with the ZAP-70 protein tyrosine kinase. We examined the contribution of the different TCR-ζ ITAMs in regulating the constitutive phosphorylation of the TCR-ζ subunit in thymocytes by analyzing TCR-ζ-deficient mice that had been reconstituted with either full-length or single ITAM-containing TCR-ζ subunits. We report in this work that in the absence of a full-length TCR-ζ subunit, there is no apparent constitutive phosphorylation of the remaining TCR/CD3 ITAMs. Following TCR ligation, all of the CD3 ITAMs become inducibly phosphorylated and associate with the ZAP-70 protein tyrosine kinase. Regardless of the number of TCR-ζ ITAMs present in the TCR complex, we report that a number of molecules involved in downstream signaling events, such as ZAP-70, SLP-76, and pp36, are all inducibly tyrosine phosphorylated following TCR ligation. These results support the notion that the different TCR ITAMs function in a quantitative rather than qualitative manner.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalJournal of Immunology
Volume160
Issue number1
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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