1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] [3].
1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2].
Nat Immunol. 2014 Feb;15(2):177-85. doi: 10.1038/ni.2790. Epub 2013 Dec 22.
T cells autoreactive to the antigen-presenting molecule CD1a 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 non-ligand-bound CD1a for testing lipids from tissues. CD1a released hundreds of ligands of two types. Inhibitory ligands were ubiquitous membrane lipids with polar head groups, whereas stimulatory compounds were apolar oils. We identified squalene and wax esters, which naturally accumulate in epidermis and sebum, as autoantigens presented by CD1a. The activation of T cells by skin oils suggested that headless mini-antigens nest within CD1a and displace non-antigenic resident lipids with large head groups. Oily autoantigens naturally coat the surface of the skin; thus, this points to a previously unknown mechanism of barrier immunity.
T 细胞自身反应性针对抗原呈递分子 CD1a 在人类血液和皮肤中很常见，但由于对 CD1 蛋白和自身脂质的背景 T 细胞反应，天然自身抗原的搜索受到了阻碍。在捕获 CD1a-脂质复合物后，我们在保留非配体结合的 CD1a 的同时轻轻洗脱配体，以用于测试来自组织的脂质。CD1a 释放了两种类型的数百种配体。抑制性配体是具有极性头部基团的普遍存在的膜脂质，而刺激性化合物是非极性油。我们确定了角鲨烯和蜡酯，它们天然存在于表皮和皮脂中，是由 CD1a 呈递的自身抗原。皮肤油激活 T 细胞表明，无头迷你抗原存在于 CD1a 内，并通过具有大头部基团的非抗原性常驻脂质取代它们。油性自身抗原自然覆盖皮肤表面；因此，这表明存在一种以前未知的屏障免疫机制。
