Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b.
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.
Loeser
Stefanie
S
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohrgasse 3, A-1030 Vienna, Austria. stefanie.loeser@imba.oeaw.ac.at
Penninger
Josef M
JM
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology* / Q000502:physiology; D006801:Humans; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases