Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
Artikel i vetenskaplig tidskrift, 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

Författare

Carl Simonsson

Göteborgs universitet

Sofia Andersson

Göteborgs universitet

Anna-Lena Stenfeldt

Göteborgs universitet

Jörgen Bergström

Göteborgs universitet

Brigitte Bauer

Göteborgs universitet

Charlotte A Jonsson

Göteborgs universitet

Marica B Ericson

Göteborgs universitet

Kerstin S Broo

The Journal of investigative dermatology

1523-1747 (ISSN)

Vol. 131 7 1486-93

Ämneskategorier

Fysikalisk kemi

Annan kemi

Farmakologi och toxikologi

DOI

10.1038/jid.2010.422

PubMed

21228815