CD152

CD152, also known as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is an inhibitory receptor of the CD28 family expressed primarily on activated T cells and at higher levels on regulatory T cells. The CTLA-4 protein is encoded by the CTLA4 gene and plays a key role in regulating immune responses and maintaining self-tolerance. It binds to the B7 family ligands, CD80 (B7-1) and CD86 (B7-2), on antigen-presenting cells with higher affinity than the costimulatory receptor CD28, thereby limiting T cell activation.

CTLA-4 functions to dampen immune responses through multiple mechanisms. By outcompeting CD28 for B7 ligands, it reduces costimulatory signals necessary for full T cell activation. In addition, CTLA-4 can mediate inhibitory signaling through its cytoplasmic tail, which contains motifs that recruit phosphatases and other signaling molecules, suppressing T cell receptor–driven signaling. A distinct model proposes that CTLA-4-expressing T cells can remove B7 ligands from APC surfaces via trans-endocytosis, effectively lowering available costimulation.

Expression of CTLA-4 is tightly regulated; it is upregulated upon T cell activation and is constitutively expressed at high levels on regulatory T cells, where it contributes to suppressive function. Genetic CTLA4 disruption in animals leads to severe autoimmunity and lymphoproliferation, and humans with CTLA4 haploinsufficiency exhibit immune dysregulation and autoimmunity.

Clinically, CTLA-4 blockade with antibodies such as ipilimumab has become a cornerstone of cancer immunotherapy by enhancing anti-tumor T cell responses, though it can cause immune-related adverse events. Therapeutic strategies also explore CTLA-4–driven agonism to treat autoimmune conditions.