CD152

CD152, also known as CTLA-4 (Cytotoxic T-Lymphocyte-Associated protein 4), is a protein receptor that plays a critical role in the immune system's regulation. It is a member of the immunoglobulin superfamily and is expressed on the surface of Helper T cells and Cytotoxic T cells. CTLA-4 is a negative regulator of T-cell activation, which makes it essential for maintaining the balance of the immune response and preventing autoimmunity.

Function

CTLA-4 acts as an "off" switch for T cells. When T cells are activated by their interaction with Antigen-Presenting Cells (APCs) through the T cell receptor (TCR) recognizing an antigen presented by the Major Histocompatibility Complex (MHC), CTLA-4 is upregulated. CTLA-4 competes with the stimulatory receptor CD28 for binding to the B7 proteins (CD80 and CD86) on the surface of APCs. CTLA-4 has a higher affinity for these ligands than CD28, effectively outcompeting it and sending an inhibitory signal to the T cell. This interaction leads to the downregulation of T cell activation, proliferation, and cytokine production.

Clinical Significance

The regulatory function of CTLA-4 has made it a target for therapeutic intervention in various diseases. Its role in downregulating immune responses is exploited in cancer immunotherapy. Drugs known as Immune Checkpoint Inhibitors, such as Ipilimumab, target CTLA-4 to block its function. This blockade prevents the "off" signal from being sent to T cells, allowing them to remain active against cancer cells for longer periods.

Conversely, the overactivation of CTLA-4 can lead to insufficient immune responses and is associated with susceptibility to infections and the development of tumors. On the other hand, genetic mutations that reduce CTLA-4 function can result in autoimmunity, where the immune system attacks the body's own tissues.

Genetics

The gene encoding CTLA-4 is located on chromosome 2 in humans. Variants of this gene have been associated with several autoimmune diseases, including Type 1 Diabetes, Rheumatoid Arthritis, and Systemic Lupus Erythematosus (SLE), suggesting its crucial role in immune regulation.

Research and Development

Research on CTLA-4 continues to be a significant area in immunology and oncology. Studies are focused on understanding its regulatory mechanisms, the balance between its inhibitory effects and those of other co-stimulatory signals, and its interactions with other immune checkpoints. This research is crucial for developing new therapies for autoimmune diseases, allergies, and cancer.