Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / physiology*
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Antigens, CD1 / metabolism
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Antigens, CD1d
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Bone Marrow Transplantation
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Cathepsin L
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Cathepsins / deficiency
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Cathepsins / genetics
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Cathepsins / physiology*
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Cell Communication
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Cell Differentiation
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Cells, Cultured
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Crosses, Genetic
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Cysteine Endopeptidases
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Endosomes / enzymology
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Endosomes / ultrastructure
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Histocompatibility Antigens Class II / immunology
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Killer Cells, Natural / chemistry
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Killer Cells, Natural / cytology*
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Ligands
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Lymphocyte Activation
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Lysosomes / enzymology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / analysis
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Radiation Chimera
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Stromal Cells / enzymology
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology*
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Thymus Gland / cytology
Substances
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Antigens, CD1
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Antigens, CD1d
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Histocompatibility Antigens Class II
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Ligands
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RNA, Messenger
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Receptors, Antigen, T-Cell, alpha-beta
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Cathepsins
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Cysteine Endopeptidases
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Cathepsin L
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Ctsl protein, mouse
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cathepsin S