Difference between revisions of "Event:272"
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== Key Event Overview == | == Key Event Overview == | ||
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=== AOPs Including This Key Event === | === AOPs Including This Key Event === | ||
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!AOP Name | !AOP Name | ||
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!Essentiality | !Essentiality | ||
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− | |[[ | + | |[[Aop:40|Covalent Protein binding leading to Skin Sensitisation]]||KE||[[Aop:40#Essentiality of the Key Events|Strong]] |
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=== Taxonomic Applicability === | === Taxonomic Applicability === | ||
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{|class="wikitable sortable" id="Specproof" | {|class="wikitable sortable" id="Specproof" | ||
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!Scientific Name | !Scientific Name | ||
!Evidence | !Evidence | ||
!Links | !Links | ||
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+ | |human||Homo sapiens||[[Event:272#Evidence Supporting Taxonomic Applicability|Strong]]||[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9606 NCBI] | ||
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+ | |mouse||Mus musculus||[[Event:272#Evidence Supporting Taxonomic Applicability|Strong]]||[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10090 NCBI] | ||
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=== Level of Biological Organization === | === Level of Biological Organization === | ||
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{|class="wikitable sortable" id="BioProof" | {|class="wikitable sortable" id="BioProof" | ||
!Biological Organization | !Biological Organization | ||
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== How this Key Event works == | == How this Key Event works == | ||
− | T-cells are typically affected by protein-hapten complexes presented by dendritic cells on MHC | + | 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<ref name="Martin 2010">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.</ref>). 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<ref name="Vocanson 2009">Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF. 2009. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64: 1699-1714.</ref>. |
− | molecules. Molecular understanding of this process has improved in recent years (see Martin | + | |
− | 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 | + | |
− | complex, the T-cell will be activated to form a memory T-cell, which subsequently proliferates. If | + | |
− | reactivated upon | + | |
− | contact dermatitis | + | |
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== How it is Measured or Detected == | == How it is Measured or Detected == | ||
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</em> | </em> | ||
− | == | + | 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<ref name="Martin 2010"></ref>. |
+ | 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<ref name="OECD 2010a">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.</ref> together with its two non-radioactive modifications (LLNA-DA TG442A<ref name="OECD 2010b">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.</ref> and LLNA-BrdU ELISA TG 442B<ref name="OECD 2010c">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.</ref>). | ||
+ | === Overview table: How it is measured or detected === | ||
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+ | {| class="wikitable" id="Event272" | ||
+ | |+ '''Overview''' | ||
+ | ! Method(s) | ||
+ | ! Reference | ||
+ | ! URL | ||
+ | ! style="text-align: center;" | Regulatory | ||
+ | |||
+ | Acceptance | ||
+ | ! style="text-align: center;" | Validated | ||
+ | ! style="text-align: center;" | Non | ||
+ | |||
+ | Validated | ||
+ | |- | ||
+ | | rowspan="3" | Local Lymph Node Assay (LLNA) | ||
+ | | TG 429 | ||
+ | | [http://www.oecd-ilibrary.org/environment/test-no-429-skin-sensitisation_9789264071100-en] | ||
+ | | rowspan="3" style="text-align: center;" | X | ||
+ | | rowspan="3" style="text-align: center;" | X | ||
+ | | rowspan="3" style="text-align: center;" | | ||
+ | |- | ||
+ | | TG 442A LLNA:DA | ||
+ | | [http://www.oecd-ilibrary.org/environment/test-no-442a-skin-sensitization_9789264090972-en] | ||
+ | |- | ||
+ | | TG 442B LLNA: BrdU-ELISA | ||
+ | | [http://www.oecd-ilibrary.org/environment/test-no-442b-skin-sensitization_9789264090996-en] | ||
+ | |} | ||
+ | |||
+ | == Evidence Supporting Taxonomic Applicability == | ||
+ | Some ''in vitro'' assays have been developed using human T cells<ref name="Martin 2010"></ref>. | ||
+ | Lymph node proliferation is the basis for the ''in vivo'' mouse LLNA. | ||
== References == | == References == | ||
<references /> | <references /> |
Latest revision as of 12:07, 27 May 2016
Contents
Event Title
Key Event Overview
Please follow link to widget page to edit this section.
If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.
AOPs Including This Key Event
AOP Name | Event Type | Essentiality |
---|---|---|
Covalent Protein binding leading to Skin Sensitisation | KE | Strong |
Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
---|---|---|---|
human | Homo sapiens | Strong | NCBI |
mouse | Mus musculus | Strong | NCBI |
Level of Biological Organization
Biological Organization |
---|
Organ |
How this Key Event works
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
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]).
Overview table: How it is measured or detected
Method(s) | Reference | URL | Regulatory
Acceptance |
Validated | Non
Validated |
---|---|---|---|---|---|
Local Lymph Node Assay (LLNA) | TG 429 | [1] | X | X | |
TG 442A LLNA:DA | [2] | ||||
TG 442B LLNA: BrdU-ELISA | [3] |
Evidence Supporting Taxonomic Applicability
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
- ↑ 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.