2. Academic Validation
  3. CD3ε recruits Numb to promote TCR degradation

CD3ε recruits Numb to promote TCR degradation

  • Int Immunol. 2016 Mar;28(3):127-37. doi: 10.1093/intimm/dxv060.
Nadia Martin-Blanco 1,  Daniel Jiménez Teja 2,  Gabriel Bretones 3,  Aldo Borroto 4,  Michael Caraballo 2,  Isabella Screpanti 5,  Javier León 3,  Balbino Alarcón 4,  Matilde Canelles 6
Affiliations

Affiliations

  • 1 Instituto de Parasitología y Biomedicina, CSIC, P. T. Ciencias de la Salud, 18100 Granada, Spain Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
  • 2 Instituto de Parasitología y Biomedicina, CSIC, P. T. Ciencias de la Salud, 18100 Granada, Spain.
  • 3 Departamento de Biología Molecular, Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC-SODERCAN, Santander, Spain.
  • 4 Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
  • 5 Laboratory of Molecular Pathology, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
  • 6 Instituto de Parasitología y Biomedicina, CSIC, P. T. Ciencias de la Salud, 18100 Granada, Spain mcanelles@ipb.csic.es.
PMID: 26507128 DOI: 10.1093/intimm/dxv060
Abstract

Modulation 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 CD3ε that overlaps with the Nck binding site. As a result, Cbl couples specifically to the CD3ε 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.

Keywords

T-cell activation; T-cell differentiation; T-cell receptor; lymphocyte signaling.

Figures