Cytotoxic T-lymphocyte associated protein 4

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4), also known as CD152 (cluster of differentiation 152), is a protein receptor that, functioning as an immune checkpoint, downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation. It acts as an "off switch" when bound to CD80 or CD86 on the surface of antigen-presenting cells.

Structure[edit | edit source]

CTLA-4 is a member of the immunoglobulin superfamily and is structurally similar to the T-cell co-stimulatory protein, CD28. It contains an extracellular V domain, a transmembrane domain, and a cytoplasmic tail. The extracellular domain is homologous to the immunoglobulin superfamily and contains a single immunoglobulin variable-like (IgV) domain.

Function[edit | edit source]

CTLA-4 plays a role in the regulation of T-cell activation. When CTLA-4 binds to B7 molecules, it inhibits the T-cell response. This is in contrast to the co-stimulatory molecule CD28, which enhances T-cell response when it binds to the same B7 molecules. Thus, CTLA-4 acts as a negative regulator of T-cell activation.

Clinical significance[edit | edit source]

CTLA-4 has been implicated in a number of diseases, including autoimmune diseases and cancer. In autoimmune diseases, the normal inhibitory function of CTLA-4 is lost, leading to uncontrolled T-cell activation and autoimmunity. In cancer, CTLA-4 is often upregulated, which can prevent the immune system from attacking the cancer cells.

Therapeutic use[edit | edit source]

CTLA-4-blocking antibodies, such as ipilimumab, have been developed for use in cancer immunotherapy. These drugs work by blocking the inhibitory effect of CTLA-4, thereby enhancing the immune response against cancer cells.

File:CTLA-4 structure.png

Structure of CTLA-4