Antigen-presenting cell
Encyclopedia
An antigen-presenting cell (APC) or accessory cell is a cell
that displays foreign antigen
complexes with major histocompatibility complex
(MHC) on their surfaces. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process
antigens and present
them to T-cells.
T cells cannot recognise, and therefore react to, 'free' antigen. T cells can only 'see' antigen that has been processed and presented by cells via an MHC molecule. Most cells in the body can present antigen to CD8+ T cells via MHC class I molecules and, thus, act as "APCs"; however, the term is often limited to those specialized cells that can prime T cells (i.e., activate a T cell that has not been exposed to antigen, termed a naive T cell
). These cells, in general, express MHC class II as well as MHC class I molecules, and can stimulate CD4+ ("helper") cells
as well as CD8+ ("cytotoxic") T cells
, respectively.
To help distinguish between the two types of APCs, those that express MHC class II molecules are often called professional antigen-presenting cells.
, and then displaying a fragment of the antigen, bound to a class II MHC
molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules is a defining feature of professional APCs.
There are three main types of professional antigen-presenting cell:
) proteins required for interaction with naive T cells; these are expressed only upon stimulation of the non-professional APC by certain cytokines such as IFN-γ. Non-professional APCs include:
s and are carried via lymph flow to the draining lymph node
s (this network is collectively known as the Lymphatic system
). The lymph nodes become a collection point to which APCs such as dendritic cells (DCs) can interact with T cells. They do this by chemotaxis
, which involves interacting with chemokine
s that are expressed on the surface of cells (e.g., endothelial cells of the high endothelial venules
) or have been released as chemical messengers to draw the APCs to the lymph nodes. During the migration, DCs undergo a process of maturation; in essence, they lose most of their ability to further engulf pathogens, and they develop an increased ability to communicate with T cells. Enzymes within the cell digest the swallowed pathogen into smaller pieces containing epitopes, which are then presented to T cells using MHC.
Recent research indicates that only certain epitopes of a pathogen are presented because they are immunodominant, it seems as a function of their binding affinity to the MHC. The stronger binding affinity allows the complex to remain kinetically stable long enough to be recognized by T cells.
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
that displays foreign antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
complexes with major histocompatibility complex
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...
(MHC) on their surfaces. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process
Antigen processing
Antigen processing is a biological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. This process involves two distinct pathways for processing of antigens from an organism's own proteins or intracellular pathogens , or from phagocytosed...
antigens and present
Antigen presentation
Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....
them to T-cells.
Types
APCs fall into two categories: professional or non-professional.T cells cannot recognise, and therefore react to, 'free' antigen. T cells can only 'see' antigen that has been processed and presented by cells via an MHC molecule. Most cells in the body can present antigen to CD8+ T cells via MHC class I molecules and, thus, act as "APCs"; however, the term is often limited to those specialized cells that can prime T cells (i.e., activate a T cell that has not been exposed to antigen, termed a naive T cell
Naive T cell
A naive T cell or Th0 cell is a T cell that has differentiated in bone marrow, and successfully undergone the positive and negative processes of central selection in the thymus...
). These cells, in general, express MHC class II as well as MHC class I molecules, and can stimulate CD4+ ("helper") cells
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
as well as CD8+ ("cytotoxic") T cells
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
, respectively.
To help distinguish between the two types of APCs, those that express MHC class II molecules are often called professional antigen-presenting cells.
Professional APCs
Professional APCs are very efficient at internalizing antigen, either by phagocytosis or by receptor-mediated endocytosisEndocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
, and then displaying a fragment of the antigen, bound to a class II 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...
molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules is a defining feature of professional APCs.
There are three main types of professional antigen-presenting cell:
- Dendritic cellDendritic cellDendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s (DCs), which have the broadest range of antigen presentation, and are probably the most important APC. Activated DCs are especially potent TH cell activators because, as part of their composition, they express co-stimulatoryCo-stimulationDuring the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.- Co-stimulation T cells require :...
molecules such as B7B7 (protein)B7 is a type of peripheral membrane protein found on activated antigen presenting cells that, when paired with either a CD28 or CD152 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...
. - MacrophageMacrophageMacrophages 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...
s, which are also CD4+ and are therefore also susceptible to infection by HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. - B-cells, which express (as B cell receptor) and secrete a specific antibody, can internalize the antigen, which bind to its BCR and present it incorporated to MHC II molecule, but are inefficient APC for most other antigens.
- Certain activated epithelial cells
Non-professional
A non-professional APC does not constitutively express the Major Histocompatibility Complex class II (MHC class IIMHC class II
MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
) proteins required for interaction with naive T cells; these are expressed only upon stimulation of the non-professional APC by certain cytokines such as IFN-γ. Non-professional APCs include:
- FibroblastFibroblastA fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s (skin) - Thymic epithelial cells
- Thyroid epithelial cellThyroid epithelial cellThyroid epithelial cells are cells in the thyroid gland that are responsible for the production and secretion of thyroid hormones, that is, thyroxine and triiodothyronine .-Function:...
s - Glial cellGlial cellGlial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s (brain) - Pancreatic beta cellBeta cellBeta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s - Vascular endothelial cells
Interaction with T cells
After APCs have phagocytosed pathogens, they usually migrate to the vast networks of lymph vesselLymph vessel
In anatomy, lymph vessels are thin walled, valved structures that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels are lined by endothelial cells, and deep to that have a thin layer of smooth muscles, and adventitia that bind...
s and are carried via lymph flow to the draining lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s (this network is collectively known as the Lymphatic system
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...
). The lymph nodes become a collection point to which APCs such as dendritic cells (DCs) can interact with T cells. They do this by chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
, which involves interacting with 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...
s that are expressed on the surface of cells (e.g., endothelial cells of the high endothelial venules
High endothelial venules
High endothelial venules are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thiner endothelial cells found in regular venules...
) or have been released as chemical messengers to draw the APCs to the lymph nodes. During the migration, DCs undergo a process of maturation; in essence, they lose most of their ability to further engulf pathogens, and they develop an increased ability to communicate with T cells. Enzymes within the cell digest the swallowed pathogen into smaller pieces containing epitopes, which are then presented to T cells using MHC.
Recent research indicates that only certain epitopes of a pathogen are presented because they are immunodominant, it seems as a function of their binding affinity to the MHC. The stronger binding affinity allows the complex to remain kinetically stable long enough to be recognized by T cells.
External links
- Antigen: protease degradation - PMAP The Proteolysis MapThe Proteolysis MapThe Proteolysis MAP is an integrated web resource focused on proteases.-Rationale:PMAP is to aid the protease researchers in reasoning about proteolytic networks and metabolic pathways.-History and funding:...
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