Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice

Immunity. 2000 Sep;13(3):355-64. doi: 10.1016/s1074-7613(00)00035-2.

Abstract

KARAP/DAP12 is a transmembrane polypeptide with an intracytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). KARAP/DAP12 is associated with several activating cell surface receptors in hematopoietic cells. Here, we report that knockin mice bearing a nonfunctional KARAP/DAP12 ITAM present altered innate immune responses. Although in these mice NK cells are present and their repertoire of inhibitory MHC class I receptors is intact, the NK cell spectrum of natural cytotoxicity toward tumor cell targets is restricted. KARAP/DAP12 loss-of-function mutant mice also exhibit a dramatic accumulation of dendritic cells in muco-cutaneous epithelia, associated with an impaired hapten-specific contact sensitivity. Thus, despite its homology with CD3zeta and FcRgamma, KARAP/DAP12 plays a specific role in innate immunity, emphasizing the nonredundancy of these ITAM-bearing polypeptides in hematopoietic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Antigens, Ly*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Crosses, Genetic
  • Cytotoxicity, Immunologic / genetics*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Epithelial Cells / immunology
  • Gene Targeting
  • Immunophenotyping
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type
  • Membrane Glycoproteins / biosynthesis
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout / immunology*
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / physiology
  • Receptors, NK Cell Lectin-Like
  • Sequence Deletion
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Skin / cytology
  • Skin / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Ly
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, NK Cell Lectin-Like
  • TYROBP protein, human