Title: Molecular docking predictions of fragrance binding to human leukocyte antigen molecules

Abstract

Abstract Background Over 4000 small chemicals have been identified as allergens capable of inducing skin sensitization. Many sensitizers are hypothesized to act as haptens producing novel antigens, which can be presented to T cells by human leukocyte antigens (HLAs). Recent studies suggest that some chemical allergens use hapten‐independent mechanisms. Objective To determine whether molecular docking can identify HLA molecules that bind skin‐sensitizing chemical allergens. Methods Structural models of HLA molecules were used as the basis for molecular docking of 22 chemical allergens. Allergens predicted to bind HLA‐B*57:01 were tested for their ability to stimulate T cells by the use of proliferation and interferon‐gamma enzyme‐linked immunospot assays. Results Chemical allergens that did not satisfy the criteria for hapten activity in vitro were predicted to bind more strongly to common HLA isoforms than those with known hapten activity. HLA‐B*57:01, which is an HLA allele required for drug hypersensitivity reactions, was predicted to bind several allergens, including benzyl benzoate, benzyl cinnamate, and benzyl salicylate. In in vitro T cell stimulation assays, benzyl salicylate and benzyl cinnamate were found to stimulate T cell responses from HLA‐B*57:01 carriers. Conclusions These data suggest that small‐molecule skin sensitizers have the potential to interact with HLA, and show that Tmore » cell‐based in vitro assays may be used to evaluate the immunogenicity of skin‐sensitizing chemicals.« less

Authors:

Schutte, Ryan J.  ^[1];

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Zhang, Xiaojuan ^[1]; An, Nan  ^[2];

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• Search DOE PAGES for ORCID "0000-0001-8962-9320"
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Ostrov, David A.  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-4696-875X"
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Vukmanović, Stanislav ^[2]

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1. Department of Pathology, Immunology, and Laboratory Medicine University of Florida College of Medicine Gainesville Florida
2. Division of Cosmetics, Office of Cosmetics and Colors, CFSAN FDA College Park Maryland

Publication Date:

2019-07-09

Sponsoring Org.:

USDOE

OSTI Identifier:

1532595

Resource Type:

Publisher's Accepted Manuscript

Journal Name:

Contact Dermatitis

Additional Journal Information:

Journal Name: Contact Dermatitis Journal Volume: 81 Journal Issue: 3; Journal ID: ISSN 0105-1873

Publisher:

Wiley-Blackwell

Country of Publication:

Denmark

Language:

English