B7 (protein)
Encyclopedia
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. Besides being present on activated APCs, B7 is also found on T-cells themselves.
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.
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.
Peripheral membrane protein
Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and...
found on activated antigen presenting cells (APC) that, when paired with either a CD28
CD28
CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells...
or CD152 (CTLA-4
CTLA-4
CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
) surface protein on a T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
, can produce a costimulatory signal to enhance or decrease the activity of a MHC
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
-TCR
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
signal between the APC and the T cell, respectively. Besides being present on activated APCs, B7 is also found on T-cells themselves.
Binding of the B7 on T-cells to CTLA-4
CTLA-4
CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
causes inhibition of the activity of T-cells.
There are two major types of B7 proteins, B7.1 and B7.2 or CD80
CD80
Cluster of Differentiation 80 is a protein found on activated B cells and monocytes that provides a costimulatory signal necessary for T cell activation and survival...
and CD86
CD86
Cluster of Differentiation 86 is a protein expressed on antigen-presenting cells that provides costimulatory signals necessary for T cell activation and survival...
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 receptorT cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
must first interact with the MHC
MHC
-Biology:*Myosin heavy chain - part of the motor protein myosin's quaternary protein structure*Major histocompatibility complex - a highly polymorphic region on chromosome 6 with genes particularly involved in immune functions-Colleges:...
molecule. This first interaction involves the CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
or CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
proteins which form a complex with the CD3
CD3
CD3 or CD-3 may be:* CD3 , an antigen, cluster of differentiation protein , part of the T cell receptor complex on a mature T lymphocyte* Ford CD3 platform* MediaMax CD-3, copy protection scheme* MiniCD, a 3-inch CD...
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
Anergy
Anergy is a term in immunobiology that describes a lack of reaction by the body's defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance. An individual in a state of anergy often indicates that the immune system is unable to mount a normal...
. The costimulatory signal necessary to continue the immune response can come from B7-CD28
CD28
CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells...
and CD40-CD40L interactions. There are other activation signals which play a role in immune responses. In the TNF
Tumor necrosis factors
Tumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...
family of molecules, the protein 4-1BB (CD137
CD137
CD137 is a member of the tumor necrosis factor receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 , 4-1BB and induced by lymphocyte activation .-Expression:...
) 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
CD28
CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells...
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
CTLA-4
CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
(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.