ζ phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists

Joaquín Madrenas, Ronald L. Wange, Jennifer L. Wang, Noah Isakov, Lawrence E. Samelson, Ronald N. Germain

Research output: Contribution to journalArticlepeer-review

503 Scopus citations

Abstract

Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones. This study examined early TCR-dependent signals induced by such partial agonists or antagonists. In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of ζ chain phosphorylation and failed to activate associated ZAP-70 kinase. These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes. This finding may explain the different biological responses to TCR occupancy by these variant ligands.

Original languageEnglish
Pages (from-to)515-518
Number of pages4
JournalScience
Volume267
Issue number5197
DOIs
StatePublished - 1 Jan 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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