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CD3 epsilon recruits Numb to promote TCR degradation

AuthorsMartín-Blanco, Nadia M. ; Jiménez Teja, Daniel; Bretones, Gabriel ; Borroto Revuelta, Aldo ; Caraballo, Michael; Screpanti, I.; Leon, Javier; Alarcón, Balbino ; Cañelles, Matilde
Keywordslymphocyte signaling
T-cell activation
T-cell differentiation
T-cell receptor
Issue DateMar-2016
PublisherOxford University Press
CitationInternational Immunology
AbstractModulation of TCR signaling upon ligand binding is achieved by changes in the equilibrium between TCR degradation, recycling and synthesis; surprisingly, the molecular mechanism of such an important process is not fully understood. Here, we describe the role of a new player in the mediation of TCR degradation: the endocytic adaptor Numb. Our data show that Numb inhibition leads to abnormal intracellular distribution and defective TCR degradation in mature T lymphocytes. In addition, we find that Numb simultaneously binds to both Cbl and a site within CD3 epsilon that overlaps with the Nck binding site. As a result, Cbl couples specifically to the CD3 epsilon chain to mediate TCR degradation. The present study unveils a novel role of Numb that lies at the heart of TCR signaling initiation and termination.
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