Antigen processing
Encyclopedia
Antigen processing is a biological process
that prepares antigen
s 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 (self) proteins or intracellular
pathogen
s (e.g. virus
es), or from phagocytosed pathogens (e.g. bacteria
); subsequent presentation of these antigens on class I or class II MHC molecules is dependent on which pathway is used. Both MHC
class I and II are required to bind antigen before they are stably expressed on a cell surface.
While the conventional distinction between the two pathways is useful, there are instances where extracellular-derived peptides are presented in the context of MHC class I and cytosolic peptides are presented in the context of MHC class II (this often happens in dendritic cells).
fragments on the cell surface on MHC class I molecules. If a virus had infected the cell, viral peptides would also be presented, allowing the immune system to recognize and kill the infected cell. Worn out proteins within the cell become ubiquitin
ated, marking them for proteasome
degradation. Proteasomes break the protein up into peptides that include some around nine amino acids long (suitable for fitting within the peptide binding cleft of MHC class I molecules). Transporter associated with antigen presenting (TAP), a protein that spans the membrane of the rough endoplasmic reticulum, transports the peptides into the lumen of the rough endoplasmic reticulum (ER). Also within the rough ER, a series of chaperone proteins, including calnexin
, calreticulin
, ERp57, and Binding immunoglobulin protein
(BiP) facilitates the proper folding of class I MHC and its association with β2 microglobulin
. The partially folded MHC class I molecule then interacts with TAP via tapasin
(the complete complex also contains calreticulin and Erp57 and, in mice, calnexin). Once the peptide is transported into the ER lumen it binds to the cleft of the awaiting MHC class I molecule, stabilizing the MHC and allowing it to be transported to the cell surface by the golgi apparatus
.
s; this process takes about an hour.
The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by Ii (the invariant chain; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then broken down in stages, leaving only a small fragment called CLIP which still blocks the peptide binding cleft. An MHC class II-like structure, HLA-DM
, removes CLIP and replaces it with a peptide from the endosome. The stable MHC class-II is then presented on the cell surface.
In Cross-presentation
, peptides derived from extracellular proteins are presented in the context of MHC class I.
Biological process
A biological process is a process of a living organism. Biological processes are made up of any number of chemical reactions or other events that results in a transformation....
that prepares 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 for presentation
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....
to special cells of the immune system
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...
called T lymphocytes
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...
. This process involves two distinct pathways for processing of antigens from an organism's own (self) proteins or intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s (e.g. virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es), or from phagocytosed pathogens (e.g. bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
); subsequent presentation of these antigens on class I or class II MHC molecules is dependent on which pathway is used. Both 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...
class I and II are required to bind antigen before they are stably expressed on a cell surface.
While the conventional distinction between the two pathways is useful, there are instances where extracellular-derived peptides are presented in the context of MHC class I and cytosolic peptides are presented in the context of MHC class II (this often happens in dendritic cells).
The Endogenous Pathway
The endogenous pathway is used to present cellular peptidePeptide
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...
fragments on the cell surface on MHC class I molecules. If a virus had infected the cell, viral peptides would also be presented, allowing the immune system to recognize and kill the infected cell. Worn out proteins within the cell become ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
ated, marking them for proteasome
Proteasome
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...
degradation. Proteasomes break the protein up into peptides that include some around nine amino acids long (suitable for fitting within the peptide binding cleft of MHC class I molecules). Transporter associated with antigen presenting (TAP), a protein that spans the membrane of the rough endoplasmic reticulum, transports the peptides into the lumen of the rough endoplasmic reticulum (ER). Also within the rough ER, a series of chaperone proteins, including calnexin
Calnexin
Calnexin is a 90kDa integral protein of the endoplasmic reticulum . It consists of a large N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short , acidic cytoplasmic tail....
, calreticulin
Calreticulin
Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 is a protein that in humans is encoded by the CALR gene....
, ERp57, and Binding immunoglobulin protein
Binding immunoglobulin protein
Binding immunoglobulin protein also known as 78 kDa glucose-regulated protein or heat shock 70 kDa protein 5 is a HSP70 molecular chaperone located in the lumen of the endoplasmic reticulum that binds newly-synthesized proteins as they are translocated into the ER, and maintains them in a state...
(BiP) facilitates the proper folding of class I MHC and its association with β2 microglobulin
Beta-2 microglobulin
β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells . In humans, the β2 microglobulin protein is encoded by the B2M gene.-Structure and function:...
. The partially folded MHC class I molecule then interacts with TAP via tapasin
Tapasin
TAP-associated glycoprotein also known as tapasin or TAPBP is a protein that in humans is encoded by the TAPBP gene.- Function :...
(the complete complex also contains calreticulin and Erp57 and, in mice, calnexin). Once the peptide is transported into the ER lumen it binds to the cleft of the awaiting MHC class I molecule, stabilizing the MHC and allowing it to be transported to the cell surface by the golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
.
The Exogenous Pathway
The exogenous pathway is utilized by specialized antigen presenting cells to present peptides derived from proteins that the cell has endocytosed. The peptides are presented on MHC class II molecules. Proteins are endocytosed and degraded by acid-dependent proteases in endosomeEndosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
s; this process takes about an hour.
The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by Ii (the invariant chain; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then broken down in stages, leaving only a small fragment called CLIP which still blocks the peptide binding cleft. An MHC class II-like structure, HLA-DM
HLA-DM
HLA-DM is an intracellular protein involved in peptide presentation by MHC class II. It is encoded by the genes and .In the endosomes, HLA-DM functions by promoting the dissociation of the CLIP peptide from MHC class II which allows endosomal peptides to bind...
, removes CLIP and replaces it with a peptide from the endosome. The stable MHC class-II is then presented on the cell surface.
In Cross-presentation
Cross-presentation
The term cross-presentation denotes the ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells . Cross-priming describes the stimulation of naive cytotoxic CD8+ T cells by this process...
, peptides derived from extracellular proteins are presented in the context of MHC class I.
See also
- Major histocompatibility complexMajor histocompatibility complexMajor 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) - T cellT cellT 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...
- Cross-presentationCross-presentationThe term cross-presentation denotes the ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells . Cross-priming describes the stimulation of naive cytotoxic CD8+ T cells by this process...
- Antigen presenting cell
- Antigen presentationAntigen presentationAntigen 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....
- Polyclonal response