This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 272

Key Event Title

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

Activation/Proliferation, T-cells

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

Explore in a Third Party Tool

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
Organ

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
lymph node

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 activation	T cell	increased
cell proliferation	memory T cell	increased

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
Skin Sensitisation AOP	KeyEvent	Undefined (send email)	Open for citation & comment	WPHA/WNT Endorsed
Covalent binding to proteins leads to Respiratory Sensitisation/Sensitization/Allergy	KeyEvent	Jessica Ponder (send email)	Under Development: Contributions and Comments Welcome	Under Development

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	High	NCBI
mouse	Mus musculus	High	NCBI

Life Stages

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

Sex Applicability

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

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

T-cells are typically affected by protein-hapten complexes presented by dendritic cells on Major Histocompatibility Complex (MHC) molecules. Molecular understanding of this process has improved in recent years (see^[1]). Briefly, MHC molecules are membrane proteins which present the small peptide antigens placed in a “groove” of the MHC molecule during its intracellular synthesis and transport to the cell surface. In the context of the MHC molecular on the cell surface, the small peptide antigen is recognized via the T-cell receptors as self or non-self (e.g. foreign). If this peptide is a foreign peptide, such as part of a protein-hapten complex, the T-cell will be activated to form a memory T-cell, which subsequently proliferates. If reactivated upon presentation by skin dendritic cells, these memory T-cells will induce allergic contact dermatitis^[2].

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

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

Most protocols recognize the importance of the process of antigen-presentation, so in vitro T-cell-based assays are typically co-cultures of allergen-treated dendritic cells and modified T-lymphocytes with expression of selected biomarkers (e.g. interferon gamma), or T-cell proliferation being the reported outcome. Much of this work has been reviewed by Martin et al^[1]. It should be remembered that lymph node cell proliferation is the basis for the in vivo mouse Local Lymph Node Assay (LLNA). OECD TG 429 is the validated test guideline for the Skin Sensitisation: Local Lymph Node Assay^[3] together with its two non-radioactive modifications (LLNA-DA TG442A^[4] and LLNA-BrdU ELISA TG 442B^[5]).

Human T cell proliferation and DC and T cell cytokine profiles produced in response to chemical respiratory stimuli have been measured in vitro. (Holden et al., 2008, Bernstein et al., 2011)

Overview table: How it is measured or detected

**Overview**
Method(s)	Reference	URL	Regulatory Acceptance	Validated
Local Lymph Node Assay (LLNA)	TG 429	[1]	X	X
	TG 442A LLNA:DA	[2]
	TG 442B LLNA: BrdU-ELISA	[3]

Domain of Applicability

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

Some in vitro assays have been developed using human T cells^[1]. Lymph node proliferation is the basis for the in vivo mouse LLNA.

References

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

↑ ^1.0 ^1.1 ^1.2 Martin SF, Esser PR, Schmucker S, Dietz L, Naisbitt DJ, Park BK, Vocanson M, Nicolas JF, Keller M, Pichler WJ, Peiser M, Luch A, Wanner R, Maggi E, Cavani A, Rustemeyer T, Richter A, Thierse HJ, Sallusto F. 2010. T-cell recognition of chemical, protein allergens and drugs; toward the development of in vitro assays. Cell. Mol. Life Sci. 67: 4171-4184.
↑ Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF. 2009. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64: 1699-1714.
↑ OECD 2010. Test No.429: Skin sensitization: Local Lymph Node Assay. OECD Guidelines for the Testing of Chemicals, Section 4: Health effects. OECD Publishing. Doi: 10.1787/9789264071100-en.
↑ OECD 2010. Test No442A: Skin sensitization: Local Lymph Node Assay:DA. OECD Guidelines for the Testing of Chemicals, Section 4: Health effects. OECD Publishing. Doi: 10.1787/9789264090972-en.
↑ OECD 2010. Test No.442B: Skin sensitization: Local Lymph Node Assay: BrdU-ELISA. OECD Guidelines for the Testing of Chemicals, Section 4: Health effects. OECD Publishing. Doi: 10.1787/9789264090996-en.

BERNSTEIN, J. A., GHOSH, D., SUBLETT, W. J., WELLS, H. & LEVIN, L. 2011. Is trimellitic anhydride skin testing a sufficient screening tool for selectively identifying TMA-exposed workers with TMA-specific serum IgE antibodies? J Occup Environ Med, 53, 1122-7.

HOLDEN, N. J., BEDFORD, P. A., MCCARTHY, N. E., MARKS, N. A., IND, P. W., JOWSEY, I. R., BASKETTER, D. A. & KNIGHT, S. C. 2008. Dendritic cells from control but not atopic donors respond to contact and respiratory sensitizer treatment in vitro with differential cytokine production and altered stimulatory capacity. Clin Exp Allergy, 38, 1148-59.