Specific T cells targeting Staphylococcus aureus fibronectin‐binding protein 1 induce a type 2/type 1 inflammatory response in sensitized atopic dermatitis patients

• Published in: Allergy (Copenhagen) 2022-04, Vol.77 (4), p.1245-1253
• Main Authors: Farag, Ahmed K., Roesner, Lennart M., Wieschowski, Susanne, Heratizadeh, Annice, Eiz‐Vesper, Britta, Kwok, William W., Valenta, Rudolf, Werfel, Thomas
• Format: Article
• Language: English
• Subjects: Antigens; antigen‐specific T cells; Atopic dermatitis; Carrier Proteins - metabolism; Cell lines; Cytokines; Cytokines - metabolism; Dermatitis; Dermatitis, Atopic; Eczema; Epitopes; Fibronectin; Fibronectins - metabolism; fibronectin‐binding protein 1; Helper cells; Histocompatibility antigen HLA; Humans; Hypersensitivity; Immunodominance; Immunoglobulin E; Lymphocytes T; Major histocompatibility complex; Original; ORIGINAL ARTICLES; Peptides; Skin; Skin diseases; Staphylococcal Infections - metabolism; Staphylococcus aureus; Virulence
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.15120

Background Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin‐binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed‐type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1‐specific T cells as possible trigger factors in AD. Methods Immunodominant T‐cell epitopes were mapped by proliferation testing of patient‐derived FBP1‐specific T‐cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA‐matched, IgE‐sensitized AD patients. Results Cytokine profiling of multimer‐sorted cells revealed that predominantly the type 2 cytokines IL‐13 and IL‐4 were secreted by these cells. In contrast, IL‐17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. Conclusions We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro‐inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients. By means of MHC multimer staining, we describe quantity and quality of FBP1‐specific T cells in patients suffering from atopic dermatitis. We demonstrate that FBP1‐specific T cells drive an allergic type 2 response in atopic dermatitis patients. Our study highlights the role of FBP1 as a microbial allergen and its potential to aggravate atopic dermatitis. Abbreviations: FACS, fluorescence‐activated cell sorting; FBP1, fibronectin‐binding protein 1; HLA‐DRB1, major histocompatibility complex, class II, DR beta 1; MHC, major histocompatibility complex, Th, T helper cell; S. aureus, Staphylococcus aureus.