CTLA-4

CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), also known as CD152, is a protein receptor that functions as an immune checkpoint and downregulates immune responses. It is a member of the immunoglobulin superfamily and is expressed on the surface of T cells. CTLA-4 is homologous to the T-cell co-stimulatory receptor CD28, but it delivers an inhibitory signal to T cells.

Structure

CTLA-4 is a type I transmembrane protein with a single extracellular immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic tail. The extracellular domain binds to B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs), which are the same ligands for CD28. However, CTLA-4 binds these ligands with higher affinity than CD28, leading to competitive inhibition.

Function

CTLA-4 plays a critical role in maintaining immune homeostasis and preventing autoimmunity. When T cells are activated, CTLA-4 is upregulated and competes with CD28 for binding to B7 molecules on APCs. This interaction transmits an inhibitory signal to the T cell, reducing its proliferation and cytokine production. This mechanism is essential for the regulation of T cell responses and the prevention of autoimmune diseases.

Clinical Significance

CTLA-4 has been implicated in various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Genetic polymorphisms in the CTLA-4 gene have been associated with susceptibility to these conditions. Additionally, CTLA-4 is a target for cancer immunotherapy. Ipilimumab, a monoclonal antibody that blocks CTLA-4, has been approved for the treatment of melanoma and is being investigated for other types of cancer. By inhibiting CTLA-4, ipilimumab enhances T cell activation and promotes anti-tumor immunity.

Research

Ongoing research is focused on understanding the precise mechanisms of CTLA-4-mediated inhibition and its role in various diseases. Studies are also exploring the potential of combining CTLA-4 blockade with other immunotherapies to improve clinical outcomes in cancer patients.

See Also

• T cell
• CD28
• B7-1
• B7-2
• Ipilimumab
• Autoimmune disease
• Cancer immunotherapy