Event:272
Contents
Event Title
Key Event Overview
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AOPs Including This Key Event
AOP Name | Event Type | Essentiality |
---|---|---|
Skin Sensitisation Initiated by Covalent Binding to Proteins | KE | Strong |
Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
---|---|---|---|
human | Homo sapiens | Strong | NCBI |
Level of Biological Organization
Biological Organization |
---|
Cellular |
How this Key Event works
T-cells are typically affected by protein-hapten complexes presented by dendritic cells on 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[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?
Recognizing the importance of the process of antigen presentation (i.e. T-cell priming), in vitro T-cell priming assays have been developed (see[3]). While first generation assays could only detect strong or extreme sensitizers, more recent development using normal human peripheral blood depleted of regulatory cells that normally prevent the sensitisation phase increased the probability that T-cell proliferation would be detected [4]. A related approach is based on the hypothesis that there is a correlation between the potency of contact allergens and T-cell frequency and T-cell receptor
repertoire[5]
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