- B7 (protein)
B7 is a type of
peripheral membrane proteinfound on activated antigen presenting cells (APC) that, when paired with either a CD28or 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-4causes inhibition of the activity of T-cells.
There are two major types of B7 proteins, B7.1 and B7.2 or
CD80and CD86respectively, however, it is not known if they differ significantly.
There are several steps to activation of the immune system against a foreign molecule. The
T cell receptormust first interact with the MHCmolecule. This first interaction involves the CD4or CD8proteins which form a complex with the CD3protein to bind to the MHCmolecule 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- CD28and CD40- CD40Linteractions. There are other activation signals which play a role in immune responses. In the TNFfamily of molecules, the protein 4-1BB( CD137) on the T cell may bind to 4-1BBLon 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
APCand is able to interact with the CD28receptor 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 CD28is 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 CD28but 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.
*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).
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