Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
Journal article, 2011
Allergic contact dermatitis (ACD) is the most prevalent form of human immunotoxicity. It is caused by skin exposure to haptens, i.e., protein-reactive, low-molecular-weight chemical compounds, which form hapten-protein complexes (HPCs) in the skin, triggering the immune system. These immunogenic HPCs are elusive. In this study a series of thiol-reactive caged fluorescent haptens, i.e., bromobimanes, were deployed in combination with two-photon fluorescence microscopy, immunohistochemistry, and proteomics to identify possible hapten targets in proteins in human skin. Key targets found were the basal keratinocytes and the keratins K5 and K14. Particularly, cysteine 54 of K5 was found to be haptenated by the bromobimanes. In addition, elevated levels of anti-keratin antibodies were found in the sera of mice exposed to bromobimanes in vivo. The results indicate a general mechanism in which thiol-reactive haptens generate cryptic epitopes normally concealed from the immune system. In addition, keratinocytes and keratin seem to have an important role in the mechanism behind ACD, which is a subject for further investigations.
Keratin-5
immunology
Fluorescent Dyes
immunology
Allergic Contact
Keratin-14
immunology
Bicyclo Compounds
Epitopes
Microscopy
Humans
analysis
immunology
Fluorescence
analysis
Haptens
Dermatitis
Author
Carl Simonsson
University of Gothenburg
Sofia Andersson
University of Gothenburg
Anna-Lena Stenfeldt
University of Gothenburg
Jörgen Bergström
University of Gothenburg
Brigitte Bauer
University of Gothenburg
Charlotte A Jonsson
University of Gothenburg
Marica B Ericson
University of Gothenburg
Kerstin S Broo
The Journal of investigative dermatology
1523-1747 (ISSN)
Vol. 131 7 1486-93Subject Categories
Physical Chemistry
Other Chemistry Topics
Pharmacology and Toxicology
DOI
10.1038/jid.2010.422
PubMed
21228815