1. Academic Validation
  2. Molecular docking predictions of fragrance binding to human leukocyte antigen molecules

Molecular docking predictions of fragrance binding to human leukocyte antigen molecules

  • Contact Dermatitis. 2019 Sep;81(3):174-183. doi: 10.1111/cod.13283.
Ryan J Schutte 1 Xiaojuan Zhang 1 Nan An 2 David A Ostrov 1 Stanislav Vukmanović 2
Affiliations

Affiliations

  • 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.
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 T cell-based in vitro assays may be used to evaluate the immunogenicity of skin-sensitizing chemicals.

Keywords

HLA; RRID:SCR_001905; T cell; fragrances; human leukocyte antigen; molecular docking; skin sensitization.

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