Journal
INTERNATIONAL IMMUNOLOGY
Volume 28, Issue 3, Pages 127-137Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxv060
Keywords
lymphocyte signaling; T-cell activation; T-cell differentiation; T-cell receptor
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Funding
- Spanish Science and Education Ministry, Special Intramural CSIC (Spanish Science Council) grant [BFU2004-01771, BFU2007-67476, BFU2010-21634]
- Excellence grant from the Department of Science and Innovation of the Regional Government of Andalucia, Spain [P06-CTS-02112]
- [SAF08-01581]
- [RD06/0020/0017]
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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 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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