A ligand for the murine NK activation receptor Ly-49D: activation of tolerized NK cells from beta 2-microglobulin-deficient mice

J Immunol. 2002 Jul 1;169(1):126-36. doi: 10.4049/jimmunol.169.1.126.

Abstract

Mouse NK cells express inhibitory NK receptors that recognize target cell MHC class I molecules and activation receptors that are less well defined. The Ly-49D activation receptor on C57BL/6 NK cells recognizes Chinese hamster ovary cells and triggers natural killing. In this study, we demonstrate that a Chinese hamster classical MHC class I molecule is the ligand for Ly-49D in a reporter gene assay system as well as in NK cell killing assays. Ly-49D recognizes the Chinese hamster class I molecule better when it is expressed with Chinese hamster beta(2)-microglobulin (beta(2)m) than murine beta(2)m. However, it is still controversial that Ly-49D recognizes H-2D(d), as we were unable to demonstrate the specificity previously reported. Using this one ligand-one receptor recognition system, function of an NK activation receptor was, for the first time, investigated in NK cells that are tolerized in beta(2)m-deficient mice. Surprisingly, Ly-49D-killing activity against ligand-expressing targets was observed with beta(2)m-deficient mouse NK cells, albeit reduced, even though "tolerized" function of Ly-49D was expected. These results indicate that Ly-49D specifically recognizes the Chinese hamster MHC class I molecule associated with Chinese hamster beta(2)m, and indicate that the Ly-49D NK cell activation receptor is not tolerized in beta(2)m deficiency.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD*
  • Antigens, Ly*
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus / genetics
  • Cricetulus / immunology*
  • Cytotoxicity Tests, Immunologic
  • Epitopes / immunology
  • Epitopes / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immune Tolerance / genetics*
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lectins, C-Type
  • Ligands
  • Lymphocyte Activation / genetics*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Rats
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, NK Cell Lectin-Like
  • Signaling Lymphocytic Activation Molecule Family
  • Species Specificity
  • Transduction, Genetic
  • beta 2-Microglobulin / deficiency*
  • beta 2-Microglobulin / genetics*

Substances

  • Antigens, CD
  • Antigens, Ly
  • CD244 protein, human
  • Cd244 protein, rat
  • Cd244a protein, mouse
  • Epitopes
  • Histocompatibility Antigens Class I
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Receptors, NK Cell Lectin-Like
  • Signaling Lymphocytic Activation Molecule Family
  • beta 2-Microglobulin

Associated data

  • GENBANK/AY064386
  • GENBANK/AY064387
  • GENBANK/AY064388
  • GENBANK/AY064389
  • GENBANK/AY064390