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2 Domain of H-2Dd Restricts the Allelic Specificity of the Murine NK Cell Inhibitory Receptor Ly-49A1
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Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden; Departments of
Microbiology and Immunology and
Medicine, University of California, San Francisco, CA 94143; and Veterans Administration Medical Center, San Francisco, CA 94121
Mouse NK lymphocytes express Ly-49 receptors, which inhibit
cytotoxicity upon ligation by specific MHC I molecules on targets.
Different members of the lectin-like mouse Ly-49 receptor family
recognize distinct subsets of murine H-2 molecules, but the molecular
basis for the allelic specificity of Ly-49 has not been defined. We
analyzed inhibition of natural killing by chimeric MHC I molecules in
which the 
1, 2, or 3
domains of the Ly-49A-binding allele H-2Dd were exchanged
for the corresponding domains of the nonbinding allele
H-2Db. Using the Ly-49A-transfected rat NK cell line,
RNK-mLy-49A.9, we demonstrated that the H-2Dd
2 domain alone accounts for allelic specificity in
protection of rat YB2/0 targets in vitro. We also showed that the
H-2Dd 2 domain is sufficient to account for
the allele-specific in vivo protection of H-2b mouse RBL-5
tumors from NK cell-mediated rejection in D8 mice. Thus, in striking
contrast to the 1 specificity of Ig-like killer
inhibitory receptors for human HLA, the lectin-like mouse Ly-49A
receptor is predominantly restricted by the H-2Dd
2 domain in vitro and in vivo.
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