Thymocyte expression of cathepsin L is essential for NKT cell development.
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.
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D016026:Bone Marrow Transplantation; D056668:Cathepsin L; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003546:Cysteine Endopeptidases; D011992:Endosomes / Q000201:enzymology / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007694:Killer Cells, Natural / Q000737:chemistry / Q000166:cytology*; D008024:Ligands; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017154:Stromal Cells / Q000201:enzymology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D013950:Thymus Gland / Q000166:cytology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S