Cytotoxic T-lymphocyte activation involves a cascade of signalling and adhesion events

Anne M. O'Rourke, Matthew F. Mescher

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

IN addition to the antigen-specific T-cell receptor (TCR), T cells bear an array of 'accessory' molecules that can contribute to stable adhesion to the antigen-bearing cell1 and provide costimulatory signals1-7. For several of these2-7, T-cell adhesion to the ligand can be activated by TCR-dependent signalling (a signal from the TCR primes the coreceptor to bind to its ligand). It is unclear whether the individual coreceptors share common mechanisms of priming and cosignalling, and perhaps act in a redundant manner, or whether they act in a distinct way and contribute uniquely to the activation process. We report here the use of isolated alloantigen, class I proteins and fibronectin ligands to show that coreceptors on cytotoxic T lymphocytes are activated sequentially and deliver distinct biochemical signals on binding to their ligands. TCR engagement activates CDS by a protein ryrosine kinasedependent pathway, and CDS then acts as a signal for initiation of polyphosphoinositide hydrolysis on binding to class I. In contrast, activated adhesion to fibronectin does not initiate polyphos- phoinositide hydrolysis, but amplifies hydrolysis once it has been initiated. Thus, cytotoxic T-lymphocyte activation involves a TCR-initiated cascade of adhesion and signalling events leading to response.

Original languageEnglish (US)
Pages (from-to)253-255
Number of pages3
JournalNature
Volume358
Issue number6383
DOIs
StatePublished - Jan 1 1992

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