CD43 regulates the threshold for T cell activation by targeting Cbl functions

T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family mem...

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Bibliographic Details
Published in:IUBMB life 2011-10, Vol.63 (10), p.940-948
Main Authors: Pedraza‐Alva, Gustavo, Mérida, Lilia B., del Rio, Roxana, Fierro, Nora A., Cruz‐Muñoz, Mario E., Olivares, Norma, Melchy, Erika, Igras, Vivian, Holländer, Georg A., Burakoff, Steven J., Rosenstein, Yvonne
Format: Article
Language:English
Subjects:
Animals
Cbl
CD43
Cell Proliferation
Humans
Immunoblotting
Immunoprecipitation
Jurkat Cells
Leukosialin - metabolism
Lymphocyte Activation - immunology
Lymphocyte Activation - physiology
Mice
Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
PKCθ
Proto-Oncogene Proteins c-cbl - metabolism
Receptors, Antigen, T-Cell - metabolism
Signal Transduction - immunology
Signal Transduction - physiology
T cell activation
T-Lymphocytes - immunology
T-Lymphocytes - physiology
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Summary:T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesired activation of T cells by regulating TCR signals. In this report, we show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement inhibits TCR‐dependent c‐Cbl tyrosine phosphorylation, c‐Cbl interaction with the adapter molecule Crk‐L and promotes Cbl‐b degradation in a PKCθ‐dependent manner. Consequently, the prolonged tyrosine phosphorylation and delayed degradation of ZAP‐70 and of the ζ chain lead to enhanced mitogen‐activated protein kinase activation and robust TC response. These data indicates that CD43‐mediated signals lower the threshold for TC activation by restricting the c‐Cbl and Cbl‐b inhibitory effects on TCR signaling. In addition to the strength and duration of intracellular signals, our data underscore temporality with which certain molecules are engaged as yet another mechanism to fine tune TC signal quality, and ultimately immune function. © 2011 IUBMB IUBMB Life, 2011
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.554