Activation of T cells: releasing the brakes by proteolytic elimination of Cbl-b.
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.
Schmitz
M Lienhard
ML
Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University Giessen, 35392 Giessen, Germany. lienhard.schmitz@biochemie.med.unigiessen.de
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; C118387:Cblb protein, mouse; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases