The rat NK cell receptors Ly49s4 and Ly49i4 recognize nonclassical MHC-I molecules on Listeria monocytogenes-infected macrophages

J Leukoc Biol. 2011 Apr;89(4):617-23. doi: 10.1189/jlb.1010593. Epub 2011 Jan 19.


Ly49 receptors in rodents, like KIRs in humans, regulate NK cell activity. Although inhibitory Ly49 receptors clearly recognize MHC-I molecules, ligands for the activating Ly49 receptors are less well defined. Here, we show that the activating Ly49s4 and the inhibitory Ly49i4 receptors recognize nonclassical MHC-I molecules on the rat macrophage cell line R2 (RT1(d)). Listeria infection of R2 macrophages led to increased expression of classical and nonclassical MHC-I molecules. Coincubation of these infected cells with reporter cells expressing Ly49i4 or Ly49s4 increased the reporter cell responses. These responses were blocked by mAb OX18 (anti-MHC-I) and AAS1 (anti-nonclassical MHC-I). IFN-γ treatment of normal R2 cells also increased the MHC-I expression and enhanced the reporter cell responses. These results suggest that activating and inhibitory Ly49 receptors monitor MHC-I expression on Listeria-infected cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Ly / immunology*
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / microbiology
  • Listeria monocytogenes / physiology*
  • Macrophages / immunology*
  • Macrophages / microbiology*
  • Rats
  • Receptors, Natural Killer Cell / immunology*


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, Ly
  • Histocompatibility Antigens Class I
  • Receptors, Natural Killer Cell