CD152 [CTLA-4] (human) (rec.) (untagged)

CD152 (Cytotoxic T-lymphocyte-associated protein 4; CTLA-4) is an inhibitory receptor belonging to the CD28 immunoglobulin subfamily, expressed primarily by T cells. Its ligands, CD80 and CD86, are typically found on the surface of antigen-presenting cells and can either bind CD28 or CTLA-4, resulting in a costimulatory or a co-inhibitory response, respectively. Because of its dampening effect, CTLA-4 is a crucial regulator of T cell homeostasis and self-tolerance.

While CD28 promotes T cell activation and proliferation, CTLA-4 is reported to dampen T cell responses through a variety of mechanisms. Prior to activation, conventional T cells (T_conv) express low levels of CTLA-4, predominantly in intracellular compartments. Upon activation, CTLA-4 expression is upregulated and becomes increasingly detectable on the cell surface. In Tregs on the other hand, transmembrane CTLA-4 is constitutively expressed and plays an important role in Treg homeostasis and function. In general, T cell CTLA-4 is largely constrained to intracellular expression although some surface expression may be detectable owing to the rapid, continuous shuttling of CTLA-4 between intracellular compartments and the plasma membrane.

Recently, CTLA-4 has been studied in dendritic cells and tumors, showing that CTLA-4 plays nonredundant and critical roles in thymic development, T cell priming, peripheral tolerance, and a variety of other critical immunoregulatory functions as an immune checkpoint in Immuno-oncology research.