B7 (protein)

B7 is a type of peripheral membrane protein found on activated antigen presenting cells (APC) that, when paired with either a CD28 or CD152 (CTLA-4) surface protein on a T cell, can produce a costimulatory signal to enhance or decrease the activity of a MHC-TCR signal between the APC and the T cell, respectively. (Coico et al. 2003) Besides being present on activated APCs, B7 is also found on T-cells themselves. (Taylor et al. 2004) Binding of the B7 on T-cells to CTLA-4 causes inhibition of the activity of T-cells.

There are two major types of B7 proteins, B7.1 and B7.2 or CD80 and CD86 respectively, however, it is not known if they differ significantly.

Costimulation

There are several steps to activation of the immune system against a foreign molecule. The T cell receptor must first interact with the MHC molecule. This first interaction involves the CD4 or CD8 proteins which form a complex with the CD3 protein to bind to the MHC molecule of the APC. This is also called "Signal 1" and its main purpose is T cell activation. However, this is insufficient for producing a T cell response by itself. In fact, lack of further stimulatory signals sends the T cell into anergy. The costimulatory signal necessary to continue the immune response can come from B7-CD28 and CD40-CD40L interactions. There are other activation signals which play a role in immune responses. In the TNF family of molecules, the protein 4-1BB (CD137) on the T cell may bind to 4-1BBL on the APC.

The primary role of the B7 proteins is to give a second signal to the T cell. The B7 (B7.1/B7.2) protein is present on the APC and is able to interact with the CD28 receptor on the T cell surface; this is also known as "Signal 2". This interaction produces a series of downstream signals which continue the cell's response, such as survival. Blockade of CD28 is effective in stopping T cell activation. The immune system takes advantage of this detail to stop immune responses. The T cell can express CTLA-4 (CD152) on its surface as well. CTLA-4 is similar to the CD28 but has 20x greater affinity for B7 proteins. However, it does not stimulate the T cell despite binding well to this receptor. As a result, the T cell is blocked from receiving the B7 protein signal and is not activated. Instead it receives an inhibitory signal which leads to downregulation of the immune response. As an illustration, mice with disrupted CTLA-4 genes are unable to stop immune responses and develop a fatal massive lymphocyte proliferation.

References

*Coico, R., Sunshine, G., and Benjamin, E. (2003). “Immunology: A Short Course 5th ed.” Pg. 131.
*Janeway, CA, Travers P, Walport M, Shlomchik MJ. (2001). "Immunobiology." 5th ed. ISBN 0-8153-3642-X.
*Taylor, P.A. et al. (2004). B7 expression on T cells down-regulates immune responses throughCTLA-4 ligation via T-T interactions. J. Immunol. 172, 34–39 (2004).