Honey Karen, Benlagha Kamel, Beers Courtney, Forbush Katherine, Teyton Luc, Kleijmeer Monique J, Rudensky Alexander Y, Bendelac Albert
Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Nat Immunol. 2002 Nov;3(11):1069-74. doi: 10.1038/ni844. Epub 2002 Oct 7.
CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V(alpha)14J(alpha)18 requires CD1d trafficking through endosomal compartments; however, the endosomal events remain undefined. We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells. In addition, catL expression in thymocytes is critical not only for selection of these cells in vivo but also for stimulation of V(alpha)14(+)NK1.1(+) T cells in vitro. CD1d cell-surface expression and intracellular localization appear normal in catL-deficient thymocytes, as does the lysosomal morphology; this implies a specific role for catL in regulating presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. These data implicate lysosomal proteases as key regulators of not only classical major histocompatibility complex class II antigen presentation but also nonclassical CD1d presentation.
向表达半不变性T细胞受体V(α)14J(α)18的自然杀伤T（NKT）细胞呈递CD1d抗原需要CD1d通过内体区室进行运输；然而，内体事件仍不明确。我们发现，缺乏内体蛋白酶组织蛋白酶L（catL）的小鼠中，V(α)14(+)NK1.1(+) T细胞数量大幅减少。此外，胸腺细胞中catL的表达不仅对这些细胞在体内的选择至关重要，而且对体外刺激V(α)14(+)NK1.1(+) T细胞也至关重要。在catL缺陷的胸腺细胞中，CD1d的细胞表面表达和细胞内定位看起来正常，溶酶体形态也是如此；这意味着catL在调节介导V(α)14(+)NK1.1(+) T细胞选择的天然CD1d配体呈递中具有特定作用。这些数据表明，溶酶体蛋白酶不仅是经典的主要组织相容性复合体II类抗原呈递的关键调节因子，也是非经典的CD1d呈递的关键调节因子。
