Question

what is the role of CTLA-4 and PD-1 in immune response?

Answer 1

Remember that in order to accomplish a specific immune response in T cells, it is important the interaction between the TCR/MHC and costimulatory proteins. The costimulatory proteins are essential for this process since they promotes clonal expansion and development of a specific effector response. The costimulatory proteins can be inhibitory or stimulating. For example, CD28 stimulates the immune response while CTL4 and PD-1 inhibits the signal.

In this context, CTLA-4 is a receptor expressed in T cells which main function is the inhibition of the T cell. Once CTLA-4 binds to its ligands (CD80 and CD86), it will send an inhibitory signal. Generally, CTLA-4 is important to control the immune response in a given scenario, preventing a excessive immune response and cell proliferation. The same situation is observed with PD-1 (Programmed death 1) which main ligands is PD-1. After 24 hours approximately after the immune response is activated, the negative costimulatory proteins such as PD-1 is expressed in order to reduce the response, preventing a chronic inflammatory response.

PD-1 and CTLA-4 are highly studied for immunotherapy against cancer. In fact, there are several antibodies that block these receptors in order to avoid the inhbitory signal and promote a much more aggressive immune response against cancer cells