title: Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
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.
authors.affiliation: Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Simonsson
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Andersson
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Stenfeldt
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergström
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bauer
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Jonsson
authors.forename: Marica B
authors.initials: MB
authors.lastname: Ericson
authors.forename: Kerstin S
authors.initials: KS
authors.lastname: Broo
mesh_terms: D001643:Bridged Bicyclo Compounds; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005456:Fluorescent Dyes; D006241:Haptens / Q000276:immunology*; D006801:Humans; D053547:Keratin-14 / Q000032:analysis / Q000276:immunology; D053555:Keratin-5 / Q000032:analysis; D008856:Microscopy, Fluorescence
chemical_list: D001643:Bridged Bicyclo Compounds; D000939:Epitopes; D005456:Fluorescent Dyes; D006241:Haptens; C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5; C028381:monobromobimane