The alpha2 domain of H-2Dd restricts the allelic specificity of the murine NK cell inhibitory receptor Ly-49A.
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 alpha1, alpha2, or alpha3 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 alpha2 domain alone accounts for allelic specificity in protection of rat YB2/0 targets in vitro. We also showed that the H-2Dd alpha2 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 alpha1 specificity of Ig-like killer inhibitory receptors for human HLA, the lectin-like mouse Ly-49A receptor is predominantly restricted by the H-2Dd alpha2 domain in vitro and in vivo.
Sundbäck
J
J
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. jonas.sundback@mtc.ki.se
Nakamura
M C
MC
Waldenström
M
M
Niemi
E C
EC
Seaman
W E
WE
Ryan
J C
JC
Kärre
K
K
D000483:Alleles; D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D000950:Antigens, Ly; D000954:Antigens, Surface; D002352:Carrier Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins