Nature Immunology
3, 1069 - 1074 (2002)
Published online: 7 October 2002; | doi:10.1038/ni844
Thymocyte expression of cathepsin L is essential for NKT cell developmentKaren Honey1, 5, Kamel Benlagha2, 5, Courtney Beers1, Katherine Forbush1, Luc Teyton3, Monique J. Kleijmeer4, Alexander Y. Rudensky1
& Albert Bendelac21
Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA. 2
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. 3
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA. 4
Department of Cell Biology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. 5
These authors contributed equally to this work.
Correspondence should be addressed to Alexander Y. Rudensky aruden@u.washington.eduCD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V 14J18 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 V14+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 V14+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 V14+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.
|
