Thymocyte expression of cathepsin L is essential for NKT cell development

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Abstract
CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor Vα14Jα18 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 Vα14+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 Vα14+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 Vα14+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.

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