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2-Microglobulin- Deficient Mice1
* Howard Hughes Medical Institute, Rheumatology Division, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110; and
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
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 
2-microglobulin (2m) than murine
2m. However, it is still controversial that Ly-49D
recognizes H-2Dd, 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
2m-deficient mice. Surprisingly, Ly-49D-killing activity
against ligand-expressing targets was observed with
2m-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 2m, and
indicate that the Ly-49D NK cell activation receptor is not tolerized
in 2m deficiency.
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