CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens.
CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens.
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CD1a 自身反应性 T 细胞在人类血液和皮肤中很常见，但对天然自身抗原的寻找却因背景 T 细胞对 CD1 蛋白和自身脂质的反应而受到干扰。捕获 CD1a-脂质复合物后，我们轻轻洗脱配体，同时保留未配体的 CD1a 用于测试组织中的脂质。 CD1a 释放了数百个两种类型的配体。抑制性配体是普遍存在的具有极性头基的膜脂，而刺激性化合物是非极性油。 CD1a 自身抗原自然积聚在表皮和皮脂中，被鉴定为角鲨烯和皮蜡。皮肤油脂对 T 细胞的激活表明，无头微型抗原嵌套在 CD1a 内，并用大头基取代非抗原驻留脂质。油性自身抗原自然覆盖在皮肤表面，这表明了一种新的屏障免疫机制。
CD1a autoreactive T cells are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids. After capturing CD1a-lipid complexes, we gently eluted ligands, while preserving unliganded CD1a for testing lipids from tissues. CD1a released hundreds of ligands of two types. Inhibitory ligands were ubiquitous membrane lipids with polar headgroups, whereas stimulatory compounds were apolar oils. CD1a autoantigens naturally accumulate in epidermis and sebum, where they were identified as squalene and skin waxes. T cell activation by skin oils suggests that headless mini-antigens nest within CD1a and displace non-antigenic resident lipids with large head groups. Oily autoantigens naturally coat the skin's surface, pointing to a new mechanism of barrier immunity.