Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), also known as CD152, is a protein receptor that plays a critical role in the regulation of the immune system. It serves as a check and balance mechanism, preventing overactivation of the immune system and averting potential damage to the body's own cells.
Function of CTLA-4
CTLA-4 is primarily expressed on the surface of T cells, and its main function is to downregulate or inhibit the immune response, acting as a 'brake' for T cells.
Upon activation by an antigen, T cells upregulate both CTLA-4 and CD28, a co-stimulatory molecule that enhances T cell responses. Both CTLA-4 and CD28 compete for binding to the same ligands, B7-1 and B7-2, which are found on antigen-presenting cells. However, CTLA-4 has a much higher affinity for these ligands and can outcompete CD28 for binding.
When CTLA-4 binds to B7-1 or B7-2, it sends an inhibitory signal to the T cell, dampening its activation and proliferation. This is in contrast to the stimulatory signal sent by CD28 when it binds to these ligands. In this way, CTLA-4 acts as a counterbalance to CD28, ensuring that the immune response is not excessively activated.
CTLA-4 in Disease and Therapy
Given its pivotal role in regulating immune responses, it is not surprising that CTLA-4 has been implicated in various diseases. For instance, genetic mutations that reduce CTLA-4 function have been linked to autoimmune conditions, where the immune system mistakenly attacks the body's own cells.
On the other hand, CTLA-4's immune-inhibitory function can be exploited by cancer cells to evade the immune system. Some cancer cells overexpress B7-1 and B7-2 ligands, engaging CTLA-4 and thereby suppressing the T cell response against them.
This has led to the development of CTLA-4-blocking antibodies, such as ipilimumab, for cancer immunotherapy. By blocking the interaction between CTLA-4 and its ligands, these drugs can 'release the brakes' on the immune system, enhancing the T cell response against cancer cells.