Cytotoxic T-Lymphocyte Associated Antigen-4 (CTLA-4), also known as CD152, is a protein receptor that plays a crucial role in the regulation of the immune system. It is a member of the immunoglobulin superfamily and functions as an immune checkpoint, downregulating immune responses . The human recombinant form of CTLA-4, tagged with an immunoglobulin G (IgG) and a histidine (His) tag, is used in various research and therapeutic applications.
CTLA-4 is expressed primarily on the surface of activated T cells and regulatory T cells (Tregs). It competes with the costimulatory receptor CD28 for binding to B7 molecules (CD80 and CD86) on antigen-presenting cells (APCs). Unlike CD28, which provides a stimulatory signal, CTLA-4 delivers an inhibitory signal that attenuates T cell activation .
The primary function of CTLA-4 is to maintain immune homeostasis and prevent autoimmunity. By inhibiting T cell activation, CTLA-4 ensures that the immune response is proportional to the threat and does not damage normal tissues . This regulatory mechanism is essential for preventing autoimmune diseases and maintaining tolerance to self-antigens.
CTLA-4 has become a significant target in cancer immunotherapy. Monoclonal antibodies that block CTLA-4, such as ipilimumab, have been developed to enhance the immune response against tumors. By inhibiting CTLA-4, these therapies aim to boost T cell activity and promote the destruction of cancer cells . Clinical trials have shown promising results, particularly in the treatment of metastatic melanoma .
The human recombinant form of CTLA-4, tagged with IgG and His, is produced using recombinant DNA technology. This form is used in research to study the protein’s structure, function, and interactions. The IgG tag facilitates purification and detection, while the His tag allows for efficient purification using metal affinity chromatography .