Releasing the Brake: Targeting Cbl-b to Enhance Lymphocyte Effector Functions

Figure 2

Cbl-b functions as central gate keeper of T-cell activation. T-cell stimulation via the TCR and the second costimulatory signal leads to the proximal activation of signaling pathway components. In the absence of costimulation, Cbl-b promotes antigen-specific T-cell tolerance. Thus, Cbl-b functions as negative regulator of the activation of T cells that can be, however, bypassed by CD28 stimulation. In the absence of Cbl-b, T cells are not dependent on a costimulatory signal and proliferative as well as cytokine response upon sole TCR-activation is comparable to WT T cell stimulated via the TCR and CD28. Note that the signaling cascades and interactions are simplified and do not show all molecules involved. For further details please refer to text. Flat-ended lines indicate inhibitory interactions. APC, antigen—presenting cell; U, Ubiquitin.