Cross-presentation
Encyclopedia
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 (cytotoxic T cells). Cross-priming describes the stimulation of naive cytotoxic CD8+ T cells by this process. This process is necessary for immunity against most tumors and against viruses that do not infect antigen-presenting cell
s.
It is also required for induction of cytotoxic immunity by vaccination
with protein antigens, for example in tumor vaccination.
Later, there had been much controversy about cross-presentation, which now is believed to have been due to particularities and limitations of some experimental systems used.
es (herpesvirus, influenzavirus, CMV
, EBV
, SIV
, papillomavirus
, and others), bacteria
(listeria, salmonella, E. coli, M. tuberculosis, and others) and tumor
s (brain, pancreas, melanoma, leukemia, and others).
Cross-priming avoids viral immune evasion strategies, such as suppression of antigen-processing. Consequently, immune responses against viruses that are able to do so, such as herpes viruses, are largely dependent on cross-presentation.
..
s, but macrophage
s, B lymphocytes and liver sinusoidal endothelial cells have also been shown to be able to do so. The intracellular mechanisms of cross-presentation are still unclear, but seem to involve specialized subcellular compartments bearing characteristics of both the endoplasmic reticulum
and the endosome
.
Endocytosed proteins are transported out of this compartment into the cytoplasm
by unknown mechanisms. There they are processed by the proteasome
into peptides, which are transported by the TAP transporter into the endoplasmic reticulum
, or back into the same endosomes , where they associate with MHC class I
molecules.
Finally, MHC class I
- peptide complexes are transported to the cell surface, where they can be detected by specific CD8 T cells.
MHC class I
MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...
molecules to CD8 T cells (cytotoxic T cells). Cross-priming describes the stimulation of naive cytotoxic CD8+ T cells by this process. This process is necessary for immunity against most tumors and against viruses that do not infect antigen-presenting cell
Antigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
s.
It is also required for induction of cytotoxic immunity by vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
with protein antigens, for example in tumor vaccination.
History
The first evidence of cross-presentation was reported 1976 by Michael J. Bevan after injection of cells carrying alloantigens into experimental animals. This resulted in CD8 T cell responses that were induced by antigen-presenting cells of the recipient, implying that these must have taken up and processed the injected cells. This observation was termed “cross-priming”.Later, there had been much controversy about cross-presentation, which now is believed to have been due to particularities and limitations of some experimental systems used.
Relevance for immunity
Cross-presentation has been shown to play a role in the immune defense against many virusVirus
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 (herpesvirus, influenzavirus, CMV
CMV
CMV is a three-letter abbreviation with multiple meanings, as described below:* Calima Aviación, ICAO airline designator* Cauliflower mosaic virus, although more commonly abbreviated as CaMV...
, EBV
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, SIV
SIV
SIV or Siv may refer to:* Simian immunodeficiency virus, a virus found in primates and related to HIV* Siv, a character in the children's fiction book series Guardians of Ga'Hoole...
, papillomavirus
Papillomavirus
Papillomaviridae is an ancient taxonomic family of non-enveloped DNA viruses, collectively known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected birds and mammals, but also a small number...
, and others), 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...
(listeria, salmonella, E. coli, M. tuberculosis, and others) and tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s (brain, pancreas, melanoma, leukemia, and others).
Cross-priming avoids viral immune evasion strategies, such as suppression of antigen-processing. Consequently, immune responses against viruses that are able to do so, such as herpes viruses, are largely dependent on cross-presentation.
Relevance for immune tolerance
Some self-antigens (autoantigens) are cross-presented, resulting in the elimination of autoreactive CD8 T cells. This mechanism to maintain self tolerance has been termed cross-toleranceCross-tolerance
Cross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to...
..
Cell biology
Antigen-presenting cells capable of cross-presentation are primarily dendritic cellDendritic 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 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...
s, B lymphocytes and liver sinusoidal endothelial cells have also been shown to be able to do so. The intracellular mechanisms of cross-presentation are still unclear, but seem to involve specialized subcellular compartments bearing characteristics of both 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...
and the endosome
Endosome
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...
.
Endocytosed proteins are transported out of this compartment into the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
by unknown mechanisms. There they are processed by the 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...
into peptides, which are transported by the TAP transporter 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...
, or back into the same endosomes , where they associate with MHC class I
MHC class I
MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...
molecules.
Finally, MHC class I
MHC class I
MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...
- peptide complexes are transported to the cell surface, where they can be detected by specific CD8 T cells.