Recruitment of Nck by CD3ε reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation

Diana Gil, Wolfgang W.A. Schamel, María Montoya, Francisco Sánchez-Madrid, Balbino Alarcón

Research output: Contribution to journalArticle

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Abstract

How membrane receptors initiate signal transduction upon ligand binding is a matter of intense scrutiny. The T cell receptor complex (TCR-CD3) is composed of TCRα/β ligand binding subunits bound to the CD3 subunits responsible for signal transduction. Although it has long been speculated that TCR-CD3 may undergo a conformational change, confirmation is still lacking. We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ε and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3ε association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.

Original languageEnglish (US)
Pages (from-to)901-912
Number of pages12
JournalCell
Volume109
Issue number7
DOIs
StatePublished - Jun 28 2002

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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