Which of the following best describes the mechanism(s) of action of CTLA-4?
CTLA-4 is an antagonistic/inhibitory receptor normally expressed by T cells that competes with CD28 for binding of B7-1 and B7-2 and thus prevents the second signal and subsequent T-cell activation. This is a key mechanism of peripheral tolerance and plays role in preventing T-cell activation against cancer cells. Administration of antibodies that bind and block CTLA-4 allows CD28 to bind B7-1 and B7-2 and mediate costimulation resulting in the augmentation of antitumor T-cell responses. This passive immunotherapy approach has been approved to treat advanced melanoma skin cancers. Signal 1 is TCR complex and co-receptor mediated. Co-stimulation (signal 2) is via CD28-B7 engagement, follows signal 1, and results in activation and proliferation. PD-1/PD-L1 are a distinct T-cell inhibitory receptor and its ligand. ZAP-70 and ITAMs are involved in intracellular T-cell activation signal transduction.
Signal 1 and costimulation
Competition and inhibition
Activation and proliferation
ZAP-70 and ITAMs
Immunology