During industrialization, humans have been exposed to increasing numbers of foreign chemicals. Failure of the immune system to tolerate drugs, cosmetics, and other skin products causes allergic contact dermatitis, a T cell-mediated disease with rising prevalence. Models of αβ T cell response emphasize T cell receptor (TCR) contact with peptide-MHC complexes, but this model cannot readily explain activation by most contact dermatitis allergens, which are nonpeptidic molecules. We tested whether CD1a, an abundant MHC I-like protein in human skin, mediates contact allergen recognition. Using CD1a-autoreactive human αβ T cell clones to screen clinically important allergens present in skin patch testing kits, we identified responses to balsam of Peru, a tree oil widely used in cosmetics and toothpaste. Additional purification identified benzyl benzoate and benzyl cinnamate as antigenic compounds within balsam of Peru. Screening of structurally related compounds revealed additional stimulants of CD1a-restricted T cells, including farnesol and coenzyme Q2. Certain general chemical features controlled response: small size, extreme hydrophobicity, and chemical constraint from rings and unsaturations. Unlike lipid antigens that protrude to form epitopes and contact TCRs, the small size of farnesol allows sequestration deeply within CD1a, where it displaces self-lipids and unmasks the CD1a surface. These studies identify molecular connections between CD1a and hypersensitivity to consumer products, defining a mechanism that could plausibly explain the many known T cell responses to oily substances.

中文翻译：

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植物提取物和商用皮肤护理产品中对CD1a和接触性皮炎过敏原的人类T细胞反应。

在工业化过程中，人类接触到越来越多的外国化学品。免疫系统不能耐受药物，化妆品和其他皮肤产品会导致过敏性接触性皮炎，这是一种由T细胞介导的疾病，发病率不断上升。αβT细胞反应的模型强调T细胞受体（TCR）与肽-MHC复合物的接触，但是该模型不能轻易解释大多数接触性皮炎变应原（非肽类分子）的激活。我们测试了CD1a（人类皮肤中丰富的MHC I样蛋白）是否介导了接触过敏原的识别。我们使用CD1a自反应性人类αβT细胞克隆筛选皮肤斑测试试剂盒中存在的临床上重要的过敏原，我们鉴定了对秘鲁香脂的反应，秘鲁香脂是一种广泛用于化妆品和牙膏中的树油。进一步纯化鉴定出苯甲酸苄酯和肉桂酸苄酯为秘鲁香脂中的抗原性化合物。结构相关化合物的筛选显示了CD1a限制性T细胞的其他刺激物，包括法尼醇和辅酶Q2。某些一般的化学特征控制了响应：小尺寸，极强的疏水性以及来自环和不饱和键的化学约束。与突出形成表位并与TCR接触的脂质抗原不同，法尼醇的小尺寸使其能够在CD1a内深处隔离，从而置换自身脂质并掩盖CD1a表面。这些研究确定了CD1a和对消费品超敏反应之间的分子联系，定义了一种机制，可以合理地解释许多已知的T细胞对油性物质的反应。