Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S

Immunity. 2001 Dec;15(6):909-19. doi: 10.1016/s1074-7613(01)00247-3.

Abstract

NK1.1(+) T cells develop and function through interactions with cell surface CD1 complexes. In I-A(b) mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of the CD1-restricted antigen, alpha-galactosylceramide (alpha-GalCer). CD1 dysfunction is secondary to defective trafficking of CD1, which colocalizes with Ii fragments and accumulates within endocytic compartments of cathepsin S(-/-) DCs. I-A(k), cathepsin S(-/-) mice do not accumulate class II-associated Ii fragments and accordingly do not display CD1 abnormalities. Thus, function of CD1 is critically linked to processing of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / physiology*
  • Antigens, CD1 / physiology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Cathepsin L
  • Cathepsins / deficiency
  • Cathepsins / genetics
  • Cathepsins / metabolism
  • Cathepsins / physiology*
  • Cell Differentiation
  • Clonal Deletion / physiology*
  • Cysteine Endopeptidases
  • Disaccharides / immunology
  • Endocytosis
  • Endosomes / metabolism
  • Galactosylceramides / immunology*
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism*
  • Hybridomas / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Killer Cells, Natural / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Transport
  • Specific Pathogen-Free Organisms
  • Superantigens / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Antigens, CD1
  • Antigens, Differentiation, B-Lymphocyte
  • Disaccharides
  • Galactosylceramides
  • Histocompatibility Antigens Class II
  • I-Ak antigen
  • Superantigens
  • invariant chain
  • Interleukin-4
  • Interferon-gamma
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin L
  • Ctsl protein, mouse
  • cathepsin S