We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tracking human contact allergens: from mass spectrometric identification of peptide-bound reactive small chemicals to chemical-specific naive human T-cell priming.
- Authors
Dietz, Lisa; Esser, Philipp R; Schmucker, Sonja S; Goette, Irina; Richter, Anne; Schnölzer, Martina; Martin, Stefan F; Thierse, Hermann-Josef
- Abstract
Modification of proteins by reactive small chemicals is a key step in the activation of chemical-specific T cells in allergic contact dermatitis (ACD). However, an integrated approach to characterize both the precise nature of chemically modified proteins and the chemical-specific T cells is currently lacking. Here, we analyze the molecular conditions for adduct formation of the strong human contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and its water-soluble form, 2,4-dinitrobenzenesulfonic acid (DNBS), with both an all amino acid-containing model peptide (± Cys) and the protein human serum albumin (HSA). Mass spectrometric detection and quantification revealed thiol-dependent peptide adduct formation at all pH values found in human skin layers. Highest modification rates were obtained with DNBS. Accordingly, DNBS- but not DNCB-modified human immature dendritic cells (iDC) induced in vitro primary human T-cell responses as did 2,4,6-trinitrobenzenesulfonic acid-modified iDC as measured by dinitrophenyl (DNP)- and trinitrophenyl (TNP)-specific T-cell proliferation and interferon gamma (IFN-γ) production in CD4(+) and CD8(+) T-cell subsets. Moreover, DNP-modified HSA protein effectively induced primary T-cell responses when processed by iDC. Thus, an integrated approach that combines efficient skin-related in chemico coupling analyses with an in vitro T-cell priming assay can be used to predict in vivo reactions of chemical contact allergens with extracellular and cellular proteins. This strategy supports the development of chemical-specific in vitro assays that are urgently required in predictive hazard identification and risk assessment of allergenic and nonallergenic chemicals.
- Publication
Toxicological sciences : an official journal of the Society of Toxicology, 2010, Vol 117, Issue 2, p336
- ISSN
1096-0929
- Publication type
Journal Article
- DOI
10.1093/toxsci/kfq209