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Event: 2275

Key Event Title

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

Gluten reactive adaptive T-cells with antigen presenting cells, co-localization

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

Co-localization of gluten reactive adaptive T-cells with APC

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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
Cellular

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
T cell

Organ term

Organ term
duodenum lamina propria

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
T cell migration	T cell	occurrence
dendritic cell migration	professional antigen presenting cell	occurrence

Key Event Overview

AOPs Including This Key Event

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AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Gluten-driven immune activation leading to celiac disease	KeyEvent	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

For the initiation of adaptive responses, the cellular components required need to be simultaneously present in lymphoid structures present in the target tissue/organ. In the case of the gastrointestinal system these lymphoid structures are the Peyer’s patches and the mesenteric lymph nodes. The relevant cellular components are professional antigen presenting cells like dendritic cells, antigen specific B cells and T cells expressing gluten-reactive T cell receptors. Both dendritic cells and antigen specific B cells can endocytose and degrade complex antigens, resulting in peptides of variable length. Upon intracellular binding of such peptide antigens to HLA-class II molecules, like HLA-DQ2.5 and HLA-DQ8, such HLA-peptide complexes will be transported to the cell surface of the antigen presenting cells, where they can be recognized by T cells expressing T cell receptors specific for the HLA-peptide complex. Thus, once all relevant cellular components are present in the lymphoid structures, the stage is set for the induction of a gluten-specific T cell response.

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

Detection methods could include the measureing of T-cell activation by T cell stimulation assays (e.g. cytokine secretion assays, cytotoxicity assay), or could also include quantification of peptide-HLA-DQ complexes by ELISA (e.g. against HLA-peptide complex) or mass spectrometry (e.g. peptide mass fingerprinting).

Domain of Applicability

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Taxonomic: Homo sapiens
Life-stage: any
Sex: Female to Male ration: approximately 2 to 1

References

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

Parham P. The Immune System, Fifth Edition. ISBN: 978-0-393-53334-7