B7 is a type of
peripheral membrane proteinPeripheral 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
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 expression is upregulated in antigen presenting cells...
or CD152 (
CTLA-4CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
) surface protein on a
T cell'T cells' 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 lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors...
, can produce a costimulatory signal to enhance or decrease the activity of a
MHCThe major histocompatibility complex is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system and autoimmunity. The diversity of MHC is important in the immune diversity in the...
-
TCRThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
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.
B7 is a type of
peripheral membrane proteinPeripheral 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
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 expression is upregulated in antigen presenting cells...
or CD152 (
CTLA-4CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
) surface protein on a
T cell'T cells' 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 lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors...
, can produce a costimulatory signal to enhance or decrease the activity of a
MHCThe major histocompatibility complex is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system and autoimmunity. The diversity of MHC is important in the immune diversity in the...
-
TCRThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
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-4CTLA4 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
CD80The protein CD80 is a molecule found on activated B cells and monocytes which provides a costimulatory signal necessary for T cell activation and survival. It is also known as B7.1....
and
CD86The protein CD86 is a molecule expressed on antigen-presenting cells that provide costimulatory signals necessary for T cell activation and survival. It is the ligand for two proteins at the cell surface of T cells, CD28 antigen and CTLA-4 . CD86 is also known as B7.2...
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 receptorThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
must first interact with the
MHC-Biology:*Myosin heavy chain - part of the motor protein myosin's quaternary protein structure-Immunology:*Major histocompatibility complex - a highly polymorphic region on chromosome 6 with genes particularly involved in immune functions-Colleges:...
molecule. This first interaction involves the
CD4CD4 is a glycoprotein expressed on the surface of T helper cells, regulatory T 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
CD8CD8 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
CD3CD3 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-Biology:*Myosin heavy chain - part of the motor protein myosin's quaternary protein structure-Immunology:*Major histocompatibility complex - a highly polymorphic region on chromosome 6 with genes particularly involved in immune functions-Colleges:...
molecule of the
APC-Biology:*Antigen-presenting cell in medicine/immunology*APC , a human gene that is classified as a tumor suppressor gene*APC , a human cancer-critical protein...
. 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
anergyAnergy 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-
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 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 family of molecules, the protein 4-1BB (
CD137CD137 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-Biology:*Antigen-presenting cell in medicine/immunology*APC , a human gene that is classified as a tumor suppressor gene*APC , a human cancer-critical protein...
.
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-Biology:*Antigen-presenting cell in medicine/immunology*APC , a human gene that is classified as a tumor suppressor gene*APC , a human cancer-critical protein...
and is able to interact with the
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 expression is upregulated in antigen presenting cells...
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
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 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-4CTLA4 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
CD28CD28 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 B7.1 and B7.2 . When activated by Toll-like receptor ligands, the B7.1 expression is upregulated in antigen presenting cells...
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.