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Event: 2254

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Gluten-reactive and transglutaminase 2 reactive B cell receptors, generation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Generation of gluten-reactive and TG2-reactive B cell receptors
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
B cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
bone marrow

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
gene conversion of immunoglobulin genes B cell receptor complex occurrence

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Gluten-driven immune activation leading to celiac disease MolecularInitiatingEvent Antonio Fernandez Dumont (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The presence of TG2-specific antibodies is a hallmark of celiac disease and is commonly used in its diagnosis of celiac disease (Fleur du Pre et al., 2020). Additionally, antibodies targeting deamidated gluten peptides are frequently detected in patients with celiac disease. The persistent production of these deamidated gluten- and TG2-reactive antibodies contributes to chronic inflammation and tissue damage in the small intestine.

For the antibody-mediated recognition of deamidated gluten and TG2, B cell receptors must be generated during B cell development. Similar to T cell receptors, this process occurs through gene rearrangement. During this process, constant and variable gene segments are joined, encoding distinct light and heavy chains. Antibodies consist of two light and two heavy chains, with a structure that includes two antigen-binding sites formed by the variable regions and a single constant region. Notably, specific variable gene segments encoding TG2-specific antibodies are consistently shared among patients with celiac disease.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Gene rearrangement itself can be detected through molecular biological techniques. In practice, however, it is much more common to detect antibodies specific for TG2 and deamidated gluten with enzyme-linked immunosorbent assay (ELISA) or rapid test kits.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Humans, with a female to male proportion of approximately 2 to 1

References

List of the literature that was cited for this KE description. More help

  • Arentz-Hansen H, Körner R, Molberg Ø, Quarsten H, Vader W, Kooy YMC, Lundin KEA, Koning F, Roepstorff P, Sollid LM, McAdam S. (2000). The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med. 191:603-612.

  • Di Niro R, Mesin L, Zheng NY, Stamnaes J, Morrissey M, Lee JH, Huang M, Iversen R, du Pré MF, Qiao SW, Lundin KE, Wilson PC, Sollid LM. (2012). High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions. Nat Med. 18:441-445.

  • du Pré MF, Blazevski J, Dewan AE, Stamnaes J, Kanduri C, Sandve GK, Johannesen MK, Lindstad CB, Hnida K, Fugger L, Melino G, Qiao SW, Sollid LM. (2020). B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2. J Exp Med. Feb 3;217(2):e20190860. doi: 10.1084/jem.20190860. 

  • Fallang LE, Bergseng E, Hotta K, Berg-Larsen A, Kim CY, Sollid LM. (2009). Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nat Immunol. 10:1096-1101.

  • Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM. (1993). Gliadin-specific, HLA-DQ(alpha 10501,beta 10201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med. 178:187-196.

  • Vader W, Kooy Y, van Veelen P, de Ru A, Harris D, Benckhuijsen W, Pena S, Mearin L, Drijfhout JW, Koning F. (2002). The gluten response in children with recent onset celiac disease. A highly diverse response towards multiple gliadin and glutenin-derived peptides. Gastroenterology. 122:1729-1737.