Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b
- ISBN: 1044-5323 (Print)\r1044-5323 (Linking)
- DOI: S1044-5323(07)00011-5 [pii]\r10.1016/j.smim.2007.02.004
- PubMed: 17391982
The family of the Casitas B-lineage Lymphoma (Cbl) proteins, c-Cbl, Cbl-b, and Cbl-3, function as E3 ubiquitin ligases and molecular adaptors. In particular, Cbl-b acts as a gatekeeper in T cell activation that controls activation thresholds and the requirement for co-stimulation. Loss of Cbl-b expression renders animals susceptible to antigen-triggered autoimmunity suggesting that Cbl-b is a key autoimmunity gene. In addition, Cbl-b plays a critical role in T cell anergy and escape from regulatory T cells (Treg) suppression. Modulation of Cbl-b might provide us with a unique opportunity for future immune treatment of human disorders such as autoimmunity, immunodeficiency, or cancer.