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E3 ubiquitin ligases as T cell anergy factors

Nature Immunology volume 5, pages 883–890 (2004)Cite this article

Abstract

E3 ubiquitin ligases have emerged as key molecular regulators of immune cell function. Three families of proteins with ubiquitin ligase activity have been described (the HECT, RING and U-box proteins), and each may be involved in the regulation of immune responses during infection by targeting specific inhibitory molecules for proteolytic destruction. Several HECT and RING E3 proteins have now also been linked to the induction and maintenance of immune self-tolerance: c-Cbl, Cbl-b, GRAIL, Itch and Nedd4 each negatively regulate T cell growth factor production and proliferation. This review will discuss the relationship between the ubiquitination of select components of the antigen-sensing signaling apparatus in T cells and the development and maintenance of the clonal anergy state.

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Figure 1: Domain organization of E3 ubiquitin ligases linked to clonal anergy.
Figure 2: Increased activation threshold in anergic T cells by RING finger–type E3 ubiquitin ligases.
Figure 3: Premature dissolution of the immunological synapse by HECT-type E3 ubiquitin ligases in anergic T cells.

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Acknowledgements

I thank R. Zhang and M. Jenkins for a critical reading of the manuscript and comments. Supported by National Institutes of Health (RO1 GM54706, PO1 AI35296 and PO1 AI50162).

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  1. Department of Medicine, Division of Rheumatic and Autoimmune Diseases, Center for Immunology, University of Minnesota Medical School, Minneapolis, 55455, Minnesota, USA

    Daniel L Mueller

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Mueller, D. E3 ubiquitin ligases as T cell anergy factors. Nat Immunol 5, 883–890 (2004). https://doi.org/10.1038/ni1106

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