Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida.
Division of Cosmetics, Office of Cosmetics and Colors, CFSAN, FDA, College Park, Maryland.
Contact Dermatitis. 2019 Sep;81(3):174-183. doi: 10.1111/cod.13283. Epub 2019 Jul 9.
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.
To determine whether molecular docking can identify HLA molecules that bind skin-sensitizing chemical allergens.
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.
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-B57:01, 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-B57:01 carriers.
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.
已鉴定出超过 4000 种小分子化学物质为能够诱导皮肤致敏的过敏原。许多敏化剂被假设为半抗原，产生新的抗原，这些抗原可以通过人类白细胞抗原（HLAs）呈递给 T 细胞。最近的研究表明，一些化学过敏原使用非半抗原依赖机制。
确定分子对接是否可以识别与皮肤致敏化学过敏原结合的 HLA 分子。
使用 HLA 分子的结构模型作为 22 种化学过敏原分子对接的基础。使用增殖和干扰素-γ酶联免疫斑点测定法测试预测与 HLA-B*57:01 结合的过敏原，以确定其刺激 T 细胞的能力。
在体外不符合半抗原活性标准的化学过敏原被预测与常见 HLA 同工型的结合强度强于具有已知半抗原活性的过敏原。HLA-B57:01 是药物过敏反应所需的 HLA 等位基因，据预测可结合多种过敏原，包括苯甲酸苄酯、肉桂酸苄酯和水杨酸苄酯。在体外 T 细胞刺激试验中，发现水杨酸苄酯和肉桂酸苄酯可刺激 HLA-B57:01 携带者的 T 细胞反应。
这些数据表明，小分子皮肤敏化剂有可能与 HLA 相互作用，并表明基于 T 细胞的体外检测可用于评估皮肤致敏化学物质的免疫原性。
