Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (CTLA-4)

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also known as CD152, is a critical inhibitory receptor and immune checkpoint molecule primarily expressed on activated T cells and regulatory T (Treg) cells [1, 5]. It belongs to the immunoglobulin superfamily and acts as a major negative regulator of T-cell responses by competing with the costimulatory receptor CD28 for binding to ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells [2, 12]. CTLA-4 possesses significantly higher affinity and avidity for these ligands than CD28 and can actively remove them from the cell surface via transendocytosis, thereby dampening T-cell activation and maintaining peripheral tolerance [5, 12, 15]. In oncology, tumor cells exploit this pathway to evade the immune system, making CTLA-4 a cornerstone target for immunotherapy; checkpoint inhibitors such as ipilimumab block its activity to enhance anti-tumor immunity [6, 9, 12]. Conversely, CTLA-4-Ig fusion proteins like abatacept are used therapeutically to suppress overactive immune responses in autoimmune conditions such as rheumatoid arthritis by preventing CD28-mediated costimulation [4, 11, 12]. While highly effective, therapeutic modulation of CTLA-4 is often associated with immune-related adverse events (irAEs), such as colitis and endocrinopathies, due to the systemic loss of immune self-tolerance [6, 14].

Other names

CD152CTLA4Cytotoxic T-lymphocyte-associated antigen 4Celiac disease 3 (CELIAC3)Insulin-dependent diabetes mellitus 12 (IDDM12)T-lymphocyte-associated antigenGSEGRD4

Immune checkpoint blockade via monoclonal antibodies to prevent inhibitory signaling and enhance anti-tumor T-cell responses, or competitive binding of B7 ligands by CTLA-4-Ig fusion proteins to inhibit CD28-mediated costimulation for immunosuppression.