Activation of T Cells: Releasing the Brakes by Proteolytic Elimination of Cbl-b

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Sci. Signal.  23 Jun 2009:
Vol. 2, Issue 76, pp. pe38
DOI: 10.1126/scisignal.276pe38

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Activation of T lymphocytes relies on the simultaneous delivery of signals from the T cell receptor and co-receptors such as CD28. The absence of co-receptor signaling leads to a state of unresponsiveness called anergy, which prevents T cells from reacting against self antigens. The biochemical program that ensures the induction of anergy uses several mechanisms, including the synthesis of ubiquitin E3 ligases such as Cbl-b (Casitas B-lineage lymphoma). Because these E3 ligases function as gatekeepers to prevent the undesired activation of T cells, full and productive induction of the T cell response requires the restriction of these negative regulators by mechanisms that we are beginning to understand.

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