Anergy Management

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Science  27 Feb 2004:
Vol. 303, Issue 5662, pp. 1261
DOI: 10.1126/science.303.5662.1261b

Preventing the unwanted activation of T lymphocytes is crucial to the well-being of an individual. One means by which this is accomplished is by exploiting the context of the signals received to permanently turn a T cell off, rather than on—a process known as anergy. Heissmeyer et al. observed that proteins involved in ubiquitination and protein degradation became more abundant in response to the sustained calcium-dependent signals that induce anergy. At the same time, two proteins that normally mediate downstream signals from the T cell receptor—phospholipase Cγ (PLCγ) and protein kinase C-θ (PKCθ—were degraded when anergic cells were restimulated. PKCθ was monoubiquitinated in anergic T cells, indicating that it might be directly targeted for degradation. Anergy and ubiquitination correlated with instability of the immune synapse: the T cell membrane-associated signaling structure. Furthermore, T cells deficient in either of two ubiquitin ligases were resistant to both anergy induction and synapse breakdown. — SJS

Nature Immunol. 10.1038/ni1047 (2004).

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