![Ramos cell trogocytosis](https://upload.wikimedia.org/wikipedia/commons/a/a8/Ramos_cell_trogocytosis.png)
Trogocytosis ( gr, trogo; ''gnaw'') is when a cell nibbles another cell. It is a process whereby
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s (
B,
T and
NK cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
) conjugated to
antigen-presenting cell
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...
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
In immunology, an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T/B cell or Natural Killer cell. The interface was originally named after the neuronal syn ...
".
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 vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
and
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
. On T cells and B cells, trogocytosis is triggered when the T cell receptor (TCR) on T cells or B cell receptor (BCR) on B cells interacts with the antigen recognized on antigen-presenting cells. Like in lymphocytes, trogocytosis occurs with
PMN (polymorphonuclear
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, also known as granulocytes) and is associated with effective
ADCC (Antibody dependent cell mediated cytotoxicity).
It was shown that in order to initiate ADCC in vitro, PMN's have to adhere to their target cells and form tight junctions with antibody
opsonized
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
tumor cells. This
cell clustering precedes mutual membrane lipid exchange between
effector
Effector may refer to:
*Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein
* ''Effector'' (album), a music album by the Experimental Techno group Download
* ''EFFector'', a publication of the El ...
and
target cell
Codocytes, also known as target cells, are red blood cells that have the appearance of a shooting target with a bullseye. In optical microscopy these cells appear to have a dark center (a central, hemoglobinized area) surrounded by a white ring ( ...
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.
Lately the term has been attributed to macrophages, such as the CNS resident microglia, which are able to partially remove small portions of neuronal axons during postnatal development.
Mechanisms of trogocytosis
Trogocytosis involves the transfer of
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
fragments from the presenting cell to the lymphocyte. Trogocytosis is specifically triggered by antigen
receptor signalling 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 or bidirectional. 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
GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 t ...
, a
G-protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
vital for common
lymphocyte functions and a prominent participant in human
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, 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
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
, increased
interferon-γ
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...
and
tumor necrosis factor-α
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing.
Physiological consequences
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 molecule
Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. Fo ...
s with
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
or
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
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
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
are highly
energetic claiming components to establish. Trogocytosis might have appeared first in very
primitive organisms to feed off other cells.
Most of the biological 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 selecting 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
Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric p ...
, a therapeutic antibody used to treat
chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
, 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 efficacy.
Epratuzumab
Epratuzumab (planned trade name LymphoCide) is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as systemic lupus erythematosus (SLE).
Clinical trials
A clinic ...
(a CD22 Mab) acts using trogocytosis to transfer CD22 and other B-cell proteins from B cells to effector cells.
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 equipment such as 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, autoimmune diseases and vaccines.
[{{cite journal , last1=Daubeuf , first1=Sandrine , last2=Préville , first2=Xavier , last3=Momot , first3=Marie , last4=Misseri , first4=Yolande , last5=Joly , first5=Etienne , last6=Hudrisier , first6=Denis , title=Improving administration regimens of CyaA-based vaccines using TRAP assays to detect antigen-specific CD8+ T cells directly ex vivo , journal=Vaccine , date=September 2009 , volume=27 , issue=41 , pages=5565–5573 , doi=10.1016/j.vaccine.2009.07.035 , pmid=19647811 ]
See also
The process of Trogocytosis is considered different from but similar to the unrelated processes known as
Phagocytosis
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
and
Paracytophagy 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. The process of paracytophagy was first descri ...
.
References
Immune system