Antigen presentation
Encyclopedia
Antigen presentation is a process in the body's immune system
by which macrophages, dendritic cells and other cell types capture antigen
s and then enable their recognition by T-cells.
The basis of adaptive immunity lies in the capacity of immune cells to distinguish between the body's own cells, and infectious pathogens.
The host’s cells express “self” antigens that identify them as such. These antigens are different from those in bacteria ("non-self" antigens) or in virally-infected host cells (“missing-self”). The ability of the adaptive immune system
to survey for infection requires specialized pathways of enabling recognition of pathogen-derived antigens by T cells.
s. The T cell receptor
is restricted
to recognizing antigenic peptides only when bound to appropriate molecules of the major histocompatibility complex
(MHC), also known in humans as Human leukocyte antigen
(HLA).
Most cells are capable of presenting antigens and activating the adaptive response. Some cells, however, are specially equipped to acquire and present antigen, and to prime naive T cells. Dendritic cells, B cells, and macrophages play a major role in the innate response, and also act as professional antigen-presenting cells (APC). These professional APCs are equipped with special immunostimulatory receptors that allow for enhanced activation of T cells.
Several different types of T cell can be activated by professional APCs, and each type of T cell is specially equipped to deal with different pathogens, whether the pathogen is bacterial, viral or a toxin. The type of T cell activated, and therefore the type of response generated, depends, in part, on the context in which the antigen was first encountered by the APC.
, into small peptide
s. A specialized carrier, the Transporter associated with Antigen Processing (TAP) complex moves the peptide into the endoplasmic reticulum
, allowing the antigenic peptide to be coupled to an MHC Class I
molecule and transported to the cell surface.
MHC Class I molecules present antigen to CD8+ cytotoxic T cell
s. With the exception of some cell types (such as erythrocytes), Class I MHC is expressed by almost all host cells. Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a population of T cells that are specialized for inducing the death of other cells. Recognition of antigenic peptides through Class I by CTLs leads to the killing of the target cell, which is infected by virus, intracytoplasmic bacterium, or are otherwise damaged or dysfunctional.
-enriched lymph nodes. During migration, DCs undergo a process of maturation in which they lose phagocytic capacity and develop an increased ability to communicate with T-cells in the lymph nodes. This maturation process is dependent on signaling from other pathogen-associated molecular pattern (PAMP) molecules through pattern recognition receptor
s, such as the members of the Toll-like receptor
family.
The DC uses lysosome
-associated enzyme
s to digest pathogen-associated proteins into smaller peptides. In the lymph node, the DC will display these antigenic peptides on its surface by coupling them to MHC Class II molecules. This MHC:antigen complex is then recognized by T cells passing through the lymph node. Exogenous antigens are usually displayed on MHC Class II
molecules, which interact with CD4+ helper T cells. CD4+ lymphocytes, or TH, are immune response mediators, and play an important role in establishing and maximizing the capabilities of the adaptive immune response.
Expression of Class II is more restricted than Class I. High levels of Class II are found on dendritic cell
s, but can also be observed on activated macrophages, B cells, and several other host cell types in inflammatory conditions.
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
by which macrophages, dendritic cells and other cell types capture 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...
s and then enable their recognition by T-cells.
The basis of adaptive immunity lies in the capacity of immune cells to distinguish between the body's own cells, and infectious pathogens.
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
to survey for infection requires specialized pathways of enabling recognition of pathogen-derived antigens by T cells.
Antigen recognition
Unlike B cells, T cells fail to recognize antigens in the absence of antigen presentation, with the important exception of the superantigenSuperantigen
Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release...
s. The T cell receptor
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...
is restricted
MHC restriction
MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell will recognize a peptide antigen only when it is bound to a host bodies' own MHC molecule...
to recognizing antigenic peptides only when bound to appropriate molecules of the 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), also known in humans as Human leukocyte antigen
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
(HLA).
Most cells are capable of presenting antigens and activating the adaptive response. Some cells, however, are specially equipped to acquire and present antigen, and to prime naive T cells. Dendritic cells, B cells, and macrophages play a major role in the innate response, and also act as professional antigen-presenting cells (APC). These professional APCs are equipped with special immunostimulatory receptors that allow for enhanced activation of T cells.
Several different types of T cell can be activated by professional APCs, and each type of T cell is specially equipped to deal with different pathogens, whether the pathogen is bacterial, viral or a toxin. The type of T cell activated, and therefore the type of response generated, depends, in part, on the context in which the antigen was first encountered by the APC.
Intracellular antigens: Class I
Intracellular antigens are produced mainly by viruses replicating within a host cell, though antigens here can also derive from cytoplasmic bacteria or the host cell's own proteins. The host cell digests cytoplasmic proteins by a specialized enzyme complex, the proteasomeProteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
, into small peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s. A specialized carrier, the Transporter associated with Antigen Processing (TAP) complex moves the peptide into the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, allowing the antigenic peptide to be coupled to an MHC Class I
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 and transported to the cell surface.
MHC Class I molecules present antigen to CD8+ cytotoxic T cell
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...
s. With the exception of some cell types (such as erythrocytes), Class I MHC is expressed by almost all host cells. Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a population of T cells that are specialized for inducing the death of other cells. Recognition of antigenic peptides through Class I by CTLs leads to the killing of the target cell, which is infected by virus, intracytoplasmic bacterium, or are otherwise damaged or dysfunctional.
Extracellular antigens: Class II
Dendritic cells (DCs) phagocytose exogenous pathogens such as bacteria, parasites, and toxins in the tissues and then migrate, via chemotactic signals, to T cellT 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...
-enriched lymph nodes. During migration, DCs undergo a process of maturation in which they lose phagocytic capacity and develop an increased ability to communicate with T-cells in the lymph nodes. This maturation process is dependent on signaling from other pathogen-associated molecular pattern (PAMP) molecules through pattern recognition receptor
Pattern recognition receptor
Pattern recognition receptors are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify pathogen-associated molecular patterns , which are associated with microbial pathogens or cellular stress, as well as damage-associated molecular...
s, such as the members of the Toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
family.
The DC uses lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
-associated enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s to digest pathogen-associated proteins into smaller peptides. In the lymph node, the DC will display these antigenic peptides on its surface by coupling them to MHC Class II molecules. This MHC:antigen complex is then recognized by T cells passing through the lymph node. Exogenous antigens are usually displayed on MHC Class II
MHC 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 ....
molecules, which interact with CD4+ helper T cells. CD4+ lymphocytes, or TH, are immune response mediators, and play an important role in establishing and maximizing the capabilities of the adaptive immune response.
Expression of Class II is more restricted than Class I. High levels of Class II are found on dendritic cell
Dendritic cell
Dendritic 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, but can also be observed on activated macrophages, B cells, and several other host cell types in inflammatory conditions.