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CTLA-4 （Cytotoxic T-Lymphocyte Antigen 4）, also known as CD152 （Cluster of Differentiation 152 is）, a protein receptor that downregulates immune responses. As a member of the immunoglobulin superfamily, CTLA-4 is expressed on the surface of helper T cells and delivers an inhibitory signal to regulate T cell activity. Structurally, the protein comprises an extracellular V domain, a transmembrane domain, and a cytoplasmic tail. Alternative splice variants of CTLA-4 produce different isoforms, including a soluble form.
CTLA-4 shares homology with the T-cell co-stimulatory protein CD28, and both molecules interact with CD80 （B7-1） and CD86 （B7-2） on antigen-presenting cells. However, they perform opposing functions: while CD28 provides a stimulatory signal, CTLA-4 delivers an inhibitory signal, making it a critical checkpoint in immune regulation. Intracellular CTLA-4 is also found in regulatory T cells and plays a role in their function.
Fusion proteins incorporating CTLA-4, such as CTLA4-Ig, have been utilized in clinical trials for conditions like rheumatoid arthritis, highlighting its potential in immunotherapy.