Trogocytosis
Encyclopedia
Trogocytosis is a process whereby lymphocyte
s (B
, T
and NK
cells
) conjugated to antigen-presenting cell
s extract surface molecules from these cells and express them on their own surface. The molecular reorganization occurring at the interface between the lymphocyte and the antigen-presenting cell during conjugation is also called “immunological synapse
”.
and in vitro
. On T and B cells cells, trogocytosis is triggered when the T cell receptor (TCR) for T cell or B cell receptor (BCR) for B cells interacts with the antigen recognized on antigen-presenting cells. Like in lymphocytes, trogocytosis occurs with PMN
(polymorphonuclear leukocytes, also known as granulocytes) and is associated with effective ADCC
(Antibody dependent cell mediated cytotoxicity).
It was shown to initiate ADCC in vitro, PMN have to adhere to their target cells so they make tight junctions with antibody opsonized tumor cells. This cell clustering
precedes mutual membrane lipid exchange between effector
and target cell
during ADCC and does not happen in the absence of opsonizing antibodies. Trogocytosis also occurs in monocytes, and dendritic cells. Outside the immune system, similar transfer of membrane fragments have been documented between sperm and oocytes, a process thought to contribute to gamete fusion.
on T and B cells, by killer inhibitory and killer activatory receptor on NK cells and by various receptors on other cells including Fc receptor and scavenger class A receptor. It is likely that trogocytosis does not involve the capture of vesicles such as exosomes secreted by antigen-presenting cells. Rather, molecules could move from antigen-presenting cells to lymphocytes conveyed by membrane nanotubes or membrane fragments could be torn by T cells due to physical forces required for immunological synapse formation and deformation. Depending on the two cell types involved in conjugates, trogocytosis can be unidirectional of bidirectionnal. Proteins transferred by trogocytosis are many and mostly include proteins inserted in or closely associated to the plasma membrane (proteins spanning the lipid bilayer or inserted in the extracellular or intracellular leaflets). For instance, human lymphocytes were recently shown to acquire the inner-membrane
protein H-Ras
, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer
, from the cells they scan. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V
by NK- and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H-RasG12V induced ERK
phosphorylation
, increased interferon-γ and tumor necrosis factor-α secretion
, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing.
or intracellular
components might alter the lymphocytes activity and direct several lymphocyte functions, such as migration to the adequate injured tissues
. Such gained plasma membrane fragments could also contribute to the capacity to proliferate
, because lipids are highly energetic claiming components to establish. Trogocytosis might have appeared first in very primitive organisms to feed off other cells.
Most of the bological functions identified for trogocytosis have been reported for lymphocytes and dendritic cells. Major findings along these lines are :
- cytotoxic T lymphocytes having captured antigenic peptide-MHC complexes can be killed by CTL specific for this antigen (a process termed « fratricide »)
- helper T lymphocyte having captured antigenic peptide-MHC complexes are involved in a negative regulatory feed-back loop leading to their inactivation
- dendritic cells stripped of antigenic peptide-MHC complexes by T cells through trogocytosis contribute to affinity maturation of T cell response by seleting high affinity T cell
- down-modulation of costimulatory molecules on dendritic cells mediated by T cells leads to regulation of T cell response
- transfer of antigen between dendritic cells by trogocytosis favours reactivation of memory T cells at the expenses of naive T cells
- transfer of antigen between dendritic cells by trogocytosis contributes to allograft rejection
.
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s (B
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...
, T
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...
and NK
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
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....
) conjugated to 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 extract surface molecules from these cells and express them on their own surface. The molecular reorganization occurring at the interface between the lymphocyte and the antigen-presenting cell during conjugation is also called “immunological synapse
Immunological synapse
In immunology, an immunological synapse is the interface between an antigen-presenting cell and a lymphocyte. It was first discovered by Abraham Kupfer at the National Jewish Medical and Research Center in Denver and the term was coined by Michael Dustin at NYU who studied it in further detail...
”.
Steps in the discovery of trogocytosis
First indication for the existence of this process dates back late 70s when several research groups reported on the presence of unexpected molecules such as Major Histocompatibility complex molecules (MHC) on T cells. The notion that membrane fragments, and not isolated molecules, could be captured by T cells on antigen-presenting cells was suggested by the capture of MHC molecules fused to the green fluorescent protein (GFP) in their intracellular portion. The demonstration that membrane fragments were involved in this transfer process came when fluorescent probes incorporated in the plasma membrane of the antigen-presenting cell as well as non-MHC molecules were found to be captured by T cells together with the antigen.Cell types performing trogocytosis
Trogocytosis has been initially documented in T, B and NK cells both in vivoIn vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
and in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. On T and B cells cells, trogocytosis is triggered when the T cell receptor (TCR) for T cell or B cell receptor (BCR) for B cells interacts with the antigen recognized on antigen-presenting cells. Like in lymphocytes, trogocytosis occurs with PMN
Granulocyte
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
(polymorphonuclear leukocytes, also known as granulocytes) and is associated with effective ADCC
Antibody-dependent cellular cytotoxicity
Antibody-Dependent Cell-Mediated Cytotoxicity is a mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune...
(Antibody dependent cell mediated cytotoxicity).
It was shown to initiate ADCC in vitro, PMN have to adhere to their target cells so they make tight junctions with antibody opsonized tumor cells. This cell clustering
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
precedes mutual membrane lipid exchange between effector
Effector (biology)
An effector is a molecule that binds to a protein and thereby alters the activity of that protein...
and target cell
Target cell
-Hematology:In hematology, target cells are very abnormal red blood cells, that have a bullseye appearance . These target cells are associated with Hemoglobin C disease, Asplenia, Liver Disease, Thalassemia and severe Iron deficiency anemia...
during ADCC and does not happen in the absence of opsonizing antibodies. Trogocytosis also occurs in monocytes, and dendritic cells. Outside the immune system, similar transfer of membrane fragments have been documented between sperm and oocytes, a process thought to contribute to gamete fusion.
Mechanisms of trogocytosis
Trogocytosis involves the transfer of plasma membrane fragments from the presenting cell to the lymphocyte. Trogocytosis is specifically triggered by antigen receptor signallingCell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
on T and B cells, by killer inhibitory and killer activatory receptor on NK cells and by various receptors on other cells including Fc receptor and scavenger class A receptor. It is likely that trogocytosis does not involve the capture of vesicles such as exosomes secreted by antigen-presenting cells. Rather, molecules could move from antigen-presenting cells to lymphocytes conveyed by membrane nanotubes or membrane fragments could be torn by T cells due to physical forces required for immunological synapse formation and deformation. Depending on the two cell types involved in conjugates, trogocytosis can be unidirectional of bidirectionnal. Proteins transferred by trogocytosis are many and mostly include proteins inserted in or closely associated to the plasma membrane (proteins spanning the lipid bilayer or inserted in the extracellular or intracellular leaflets). For instance, human lymphocytes were recently shown to acquire the inner-membrane
Inner membrane
The inner membrane is the biological membrane of an organelle or Gram-negative bacteria that is within an outer membrane....
protein H-Ras
HRAS
GTPase HRas also known as transforming protein p21 is an enzyme that in humans is encoded by the HRAS gene. The HRAS gene is located on the short arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549.- Function :...
, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, from the cells they scan. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V
HRAS
GTPase HRas also known as transforming protein p21 is an enzyme that in humans is encoded by the HRAS gene. The HRAS gene is located on the short arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549.- Function :...
by NK- and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H-RasG12V induced ERK
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, increased interferon-γ and tumor necrosis factor-α secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing.
Physiological consequences of trogocytosis
Trogocytosis can have physiological consequences in two ways : either because "recipient" cells acquire and make use of molecules they do not usually express or because « donor » cells are stripped of molecules, which may alter their interaction with cellular partners. Acquired molecules, such as regulatory molecules with extracellularExtracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
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...
components might alter the lymphocytes activity and direct several lymphocyte functions, such as migration to the adequate injured tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
. Such gained plasma membrane fragments could also contribute to the capacity to proliferate
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, because lipids are highly energetic claiming components to establish. Trogocytosis might have appeared first in very primitive organisms to feed off other cells.
Most of the bological functions identified for trogocytosis have been reported for lymphocytes and dendritic cells. Major findings along these lines are :
- cytotoxic T lymphocytes having captured antigenic peptide-MHC complexes can be killed by CTL specific for this antigen (a process termed « fratricide »)
- helper T lymphocyte having captured antigenic peptide-MHC complexes are involved in a negative regulatory feed-back loop leading to their inactivation
- dendritic cells stripped of antigenic peptide-MHC complexes by T cells through trogocytosis contribute to affinity maturation of T cell response by seleting high affinity T cell
- down-modulation of costimulatory molecules on dendritic cells mediated by T cells leads to regulation of T cell response
- transfer of antigen between dendritic cells by trogocytosis favours reactivation of memory T cells at the expenses of naive T cells
- transfer of antigen between dendritic cells by trogocytosis contributes to allograft rejection
Implications of trogocytosis in serotherapeutic approaches
Therapeutic antibodies can be used to treat cancer. An example is rituximab, a therapeutic antibody used to treat chronic lymphocytic leukemia recognizes the CD20 molecule expressed by tumor cells and leads to their elimination. However, using too much of the antibody results in part from the removal of rituximab-CD20 complexes from the tumor cell surface by monocytes through trogocytosis. This effect leads to tumors cell escape by antigenic modulation. Reducing the dose of therapeutic antibodies to limit the extent of trogocytosis might improve their therapeutic efficay.Trogocytosis-based assays as immunomonitoring tools
TRAP assays (TRogocytosis Analysis Protocol) allow to identify, characterize and purify T and B cells recognizing their specific antigen based on their ability to extract molecules (in that case, fluorescent probes) from the plasma membrane of antigen-presenting cells. These assays require as an equipment a flow cytometer but are otherwise very cheap, easy to perform, fast (can be performed within 3 hours) and applicable to any population of T or B cells. TRAP assays have been successfully used to detect T cell responses against viral infections, cancer, auto-immune diseases and vaccines.See also
The process of Trogocytosis is considered different from similar but unrelated processes such as Phagocytosis and ParacytophagyParacytophagy
Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells...
.