B7 (protein)
B7 is a type of
There are two major types of B7 proteins: B7-1 or CD80, and B7-2 or CD86. It is not known if they differ significantly from each other. So far
Costimulation
There are several steps to activation of the immune system against a pathogen. The T-cell receptor must first interact with the Major histocompatibility complex (MHC) surface protein. The CD4 or CD8 proteins on the T-cell surface form a complex with the CD3 protein, which can then recognize the MHC. This is also called "Signal 1" and its main purpose is to guarantee antigen specificity of the T cell activation.
However, MHC binding itself is insufficient for producing a T cell response. In fact, lack of further stimulatory signals sends the T cell into
When CD40 on the APC binds CD40L(CD154) on the T cell, signals are sent back to both the APC and the T cell. (1) The signal from the APC to the T cell informs the T cell that it must express CD28 on its surface. (2) The signal from the T cell to the APC informs the APC to express B7 (which can be either B7.1 or B7.2). It is the B7-CD28 interaction that leads to activation of the T cell. Importantly, the B7-CD28 binding additionally instructs the T cell to produce CTLA-4 (the competitor for CD28). Since CTLA-4 also binds to B7 it decreases the B7 that can bind to CD28. The B7-CTLA-4 binding suppresses T cell activation. The balance between the opposing signals generated by B7-CD28 and B7-CTLA-4 binding regulates the intensity of the T cell response.
There are other activation signals which play a role in immune responses. In the
The B7 (B7-1/B7-2) protein is present on the APC surface, and it interacts with the CD28 receptor on the T cell surface. This is one source of "Signal 2" (cytokines can also contribute to T-cell activation, called "Signal 3"). This interaction produces a series of downstream signals which promote the target T cell's survival and activation.
Blockade of
Members of the family
Apart from B7-1 and B7-2, there are other proteins grouped in the B7 family, as summarized in the following table.
Name | Alternative names | Binds to |
---|---|---|
B7-1 | CD80 | CTLA-4, PD-L1
|
B7-2 | CD86 | CTLA-4
|
B7-DC | PDCD1LG2, PD-L2, CD273 | PD-1
|
B7-H1 | PD-L1, CD274 | PD-1
|
B7-H2 | ICOSLG, B7RP1, CD275 | ICOS |
B7-H3 | CD276 | |
B7-H4 | VTCN1 | |
B7-H5 | VISTA, Platelet receptor Gi24, SISP1 | |
B7-H6 | NCR3LG1 | NKp30
|
B7-H7 | HHLA2 | CD28H |
References
B7-1 and B7-2 have a similar organization of extracellular domains but differ in cytosolic domains.