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Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.

Journal article
Authors Carl Simonsson
Sofia Andersson
Anna-Lena Stenfeldt
Jörgen Bergström
Brigitte Bauer
Charlotte A Jonsson
Marica B Ericson
Kerstin S Broo
Published in The Journal of investigative dermatology
Volume 131
Issue 7
Pages 1486-93
ISSN 1523-1747
Publication year 2011
Published at Department of Chemistry
Core Facilities, Proteomics
Department of Physics (GU)
Pages 1486-93
Language en
Links dx.doi.org/10.1038/jid.2010.422
Keywords Bicyclo Compounds, Dermatitis, Allergic Contact, immunology, Epitopes, immunology, Fluorescent Dyes, Haptens, immunology, Humans, Keratin-14, analysis, immunology, Keratin-5, analysis, Microscopy, Fluorescence
Subject categories Spectroscopy, Other Chemistry Topics, Toxicology

Abstract

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.

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