Cytotoxic T-Lymphocyte Associated Antigen-4 (CTLA-4), also known as CD152, is a protein receptor that plays a crucial role in the immune system. It is a member of the immunoglobulin superfamily and is expressed on the surface of T cells. CTLA-4 functions as an immune checkpoint, providing inhibitory signals to T cells, which are essential for maintaining immune homeostasis and preventing autoimmunity .
CTLA-4 shares structural similarities with CD28, another receptor on T cells, and both receptors bind to the same ligands, CD80 and CD86, on antigen-presenting cells (APCs). However, while CD28 provides stimulatory signals to T cells, CTLA-4 delivers inhibitory signals. This antagonistic relationship is critical for regulating T cell activation and ensuring that the immune response is appropriately controlled .
The primary mechanism by which CTLA-4 inhibits T cell activation involves its higher affinity for CD80 and CD86 compared to CD28. By outcompeting CD28 for these ligands, CTLA-4 effectively reduces the co-stimulatory signals required for full T cell activation. This inhibition is crucial for preventing excessive immune responses that could lead to tissue damage and autoimmune diseases .
CTLA-4 has become a significant target in immunotherapy, particularly in the treatment of cancer. Blocking CTLA-4 with monoclonal antibodies, such as ipilimumab, can enhance T cell activation and promote anti-tumor immunity. This approach has shown promising results in treating various cancers, including melanoma . Additionally, CTLA-4-Ig (abatacept) is used in the treatment of autoimmune diseases like rheumatoid arthritis by inhibiting T cell activation and reducing inflammation .
Ongoing research aims to further understand the intricate mechanisms of CTLA-4 and optimize its therapeutic potential. Studies are exploring the effects of CTLA-4 on different immune cell types, including B cells, and its role in various disease contexts. For instance, CTLA-4-Ig has been shown to suppress the expression of activation markers and pro-inflammatory cytokines in human B cells, highlighting its broader immunomodulatory effects .