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Thymocyte expression of cathepsin L is essential for NKT cell development

Academic Article
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Overview

authors

  • Honey, K.
  • Benlagha, K.
  • Beers, C.
  • Forbush, K.
  • Teyton, Luc
  • Kleijmeer, M. J.
  • Rudensky, A. Y.
  • Bendelac, A.

publication date

  • November 2002

journal

  • Nature Immunology  Journal

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.

subject areas

  • Animals
  • Antigen Presentation
  • Antigens, CD1
  • Antigens, CD1d
  • Bone Marrow Transplantation
  • Cathepsin L
  • Cathepsins
  • Cell Communication
  • Cell Differentiation
  • Cells, Cultured
  • Crosses, Genetic
  • Cysteine Endopeptidases
  • Endosomes
  • Histocompatibility Antigens Class II
  • Killer Cells, Natural
  • Ligands
  • Lymphocyte Activation
  • Lysosomes
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger
  • Radiation Chimera
  • Receptors, Antigen, T-Cell, alpha-beta
  • Stromal Cells
  • T-Lymphocytes
  • Thymus Gland
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Identity

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni844

PubMed ID

  • 12368909
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Additional Document Info

start page

  • 1069

end page

  • 1074

volume

  • 3

issue

  • 11

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