CD154
Encyclopedia
CD154, also called CD40 ligand or CD40L, is a protein
that is primarily expressed on activated T cells and is a member of the TNF
superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In general, CD40L plays the role of a costimulatory molecule and induces activation in APC in association with T cell receptor stimulation by MHC molecules on the APC. In total CD40L has three binding partners: CD40, α5β1
integrin and αIIbβ3.
CD154 is expressed on the surface of T cell
s. It regulates B cell
function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper IgM syndrome
.
, the primary signal for activation is IFN-γ
from Th1 type CD4
T cell
s. The secondary signal is CD40L on the T cell, which binds CD40 on the macrophage
cell surface. As a result, the macrophage expresses more CD40 and TNF
receptors on its surface, which helps increase the level of activation. The activated macrophage can then destroy phagocytosed bacteria and produce more cytokines.
can present antigens to helper T cells. If the T cell
recognizes the peptide presented by the B cell, the T cell synthesizes CD40L. The CD40L binds to the B cell's CD40 receptor, causing resting B cell activation. The T cell also produces IL-4, which directly binds to B cell receptors. As a result of this interaction, the B cell can undergo division, antibody
isotype switching, and differentiation to plasma cell
s. The end-result is a B cell that is able to mass-produce specific antibodies against an antigenic target.
s) leads to reactive oxygen species
production, as well as chemokine
and cytokine
production, and expression of adhesion molecules
such as E-selectin
, ICAM-1
, and VCAM-1
. This inflammatory reaction in endothelial cells promotes recruitment of leukocytes
to lesions and may potentially promote atherogenesis
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that is primarily expressed on activated T cells and is a member of 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:...
superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In general, CD40L plays the role of a costimulatory molecule and induces activation in APC in association with T cell receptor stimulation by MHC molecules on the APC. In total CD40L has three binding partners: CD40, α5β1
Alpha-5 beta-1
α5β1 is an integrin that binds to matrix macromolecules and proteinases and thereby stimulates angiogenesis. It is composed of α5 and β1 subunits. It is the primary receptor for fibronectin...
integrin and αIIbβ3.
CD154 is expressed on the surface of 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...
s. It regulates B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper IgM syndrome
Hyper IgM syndrome
Hyper IgM syndrome is a family of genetic disorders in which the level of Immunoglobulin M antibodies is relatively high. The most common type is a result of a defect in a Th2 cell protein . The disorder causes immunodeficiencies, including a higher than normal susceptibility to various types of...
.
Expression of CD154
CD40 ligand is primarily expressed on activated CD4+ T lymphocytes but is also found in a soluble form. While CD40L was originally described on T lymphocytes, its expression has since been found on a wide variety of cells, including platelets, mast cells, macrophages, basophils, NK cells, B lymphocytes, as well as non-haematopoietic cells (smooth muscle cells, endothelial cells, and epithelial cells).Macrophages
In the macrophageMacrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
, the primary signal for activation is IFN-γ
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
from Th1 type 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...
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...
s. The secondary signal is CD40L on the T cell, which binds CD40 on the macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
cell surface. As a result, the macrophage expresses more CD40 and 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:...
receptors on its surface, which helps increase the level of activation. The activated macrophage can then destroy phagocytosed bacteria and produce more cytokines.
B cells
The B cellB cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
can present antigens to helper T cells. If the 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...
recognizes the peptide presented by the B cell, the T cell synthesizes CD40L. The CD40L binds to the B cell's CD40 receptor, causing resting B cell activation. The T cell also produces IL-4, which directly binds to B cell receptors. As a result of this interaction, the B cell can undergo division, antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
isotype switching, and differentiation to plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
s. The end-result is a B cell that is able to mass-produce specific antibodies against an antigenic target.
Endothelial cells
Activation of endothelial cells by CD40L (e.g. from activated plateletPlatelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s) leads to reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
production, as well as chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
and cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
production, and expression of adhesion molecules
Cell adhesion molecule
Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
such as E-selectin
E-selectin
E-selectin, also known as CD62 antigen-like family member E , endothelial-leukocyte adhesion molecule 1 , or leukocyte-endothelial cell adhesion molecule 2 , is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in...
, ICAM-1
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
, and VCAM-1
VCAM-1
Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 or cluster of differentiation 106 is a protein that in humans is encoded by the VCAM1 gene...
. This inflammatory reaction in endothelial cells promotes recruitment of leukocytes
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
to lesions and may potentially promote atherogenesis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
.