What happens when CTLA-4 is blocked?
Some anticancer drugs, called immune checkpoint inhibitors, are used to block CTLA-4. When this protein is blocked, the “brakes” on the immune system are released and the ability of T cells to kill cancer cells is increased.
What is the function of CTLA-4 expression on T cells?
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance.
What does CTLA-4 compete with?
CTLA-4 competes with CD28 for B7 binding and interacts with clathrin adaptor proteins and tyrosine phosphatases via its cytoplasmic domain to control cell trafficking and set the activation threshold in T cells. CTLA-4 is essential for regulatory T cell function.
What is CTLA-4 expressed?
CTLA-4 is a molecule expressed on T cells after activation and strongly binds to co-stimulatory molecules on antigen-presenting cells that prevent binding of these molecules needed for T-cell activation. The CTLA-4 molecule acts as a halting mechanism, decreasing the function of T cells.
Does CTLA-4 inhibit T cells?
Together, these data suggest that CTLA-4 and PD-1 inhibit T-cell activation through distinct and potentially synergistic mechanisms. Precise regulation of T-lymphocyte proliferation is critical to the acquired immune response and hematopoietic homeostasis.
What does CTLA-4 bind?
CTLA-4 binds to CD80 and CD86 with higher affinity and avidity than does CD28, preventing Tcon stimulation through CD80/CD86 interaction with CD28. Removal of CD80/CD86 ligands by trans-endocytosis results in impaired costimulation of T cells via CD28, resulting in immune regulation.
Is CTLA-4 expressed on tumor cells?
CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer.