The constitutive tyrosine phosphorylation of CD3ζ results from TCR-MHC interactions that are independent of thymic selection

Amy M. Becker, Laura M. DeFord-Watts, Christoph Wuelfing, Nicolai S C Van Oers

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The TCR complex, when isolated from thymocytes and peripheral T cells, contains a constitutively tyrosine-phosphorylated CD3ζ molecule termed p21. Previous investigations have shown that the constitutive phosphorylation of CD3ζ results from TCR interactions with MHC molecules occurring in both the thymus and the periphery. To determine what contribution the selection environment had on this constitutive phosphorylation, we analyzed CB3ζ from several distinct class I- and II-restricted TCR-transgenic mice where thymocyte development occurred in either a selecting or a nonselecting MHC environment. Herein, we report that constitutively phosphorylated CB3ζ (p21) was present in thymocytes that developed under nonselecting peptide-MHC conditions. These findings strongly support the model that the TCR has an inherent avidity for MHC molecules before repertoire selection. Biochemical analyses of the TCR complex before and after TCR stimulation suggested that the constitutively phosphorylated CD3ζ subunit did not contribute to de novo TCR signals. These findings may have important implications for T cell functions during self-MHC recognition under normal and autoimmune circumstances.

Original languageEnglish (US)
Pages (from-to)4120-4128
Number of pages9
JournalJournal of Immunology
Volume178
Issue number7
DOIs
StatePublished - Apr 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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