Ly-49s3 is a promiscuous activating rat NK cell receptor for nonclassical MHC class I-encoded target ligands.
Previous studies of the rapid rejection of MHC-disparate lymphocytes in rats, named allogeneic lymphocyte cytotoxicity, have indicated that rat NK cells express activating receptors for nonclassical MHC class I allodeterminants from the RT1-C/E/M region. Using an expression cloning system that identifies activating receptors associated with the transmembrane adapter molecule DAP12, we have cloned a novel rat Ly-49 receptor that we have termed Ly-49 stimulatory receptor 3 (Ly-49s3). A newly generated anti-Ly-49s3 Ab, mAb DAR13, identified subpopulations of resting and IL-2-activated NK cells, but not T or B lymphocytes. Depletion of Ly-49s3-expressing NK cells drastically reduced alloreactivity in vitro, indicating that this subpopulation is responsible for a major part of the observed NK alloreactivity. DAR13-mediated blockade of Ly-49s3 inhibited killing of MHC-congenic target cells from the av1, n, lv1, and c haplotypes, but not from the u or b haplotypes. A putative ligand was mapped to the nonclassical MHC class I region (RT1-C/E/M) using intra-MHC recombinant strains. Relative numbers of Ly-49s3(+) NK cells were reduced, and surface levels of Ly-49s3 were lower, in MHC congenic strains expressing the putative Ly-49s3 ligand(s). In conclusion, we have identified a novel Ly-49 receptor that triggers rat NK cell-mediated responses.
Naper
Christian
C
Veterans Affairs Medical Center, Northern California Institute for Research and Education, and University of California, San Francisco, CA 94121, USA.
Hayashi
Shigenari
S
Kveberg
Lise
L
Niemi
Eréne C
EC
Lanier
Lewis L
LL
Vaage
John T
JT
Ryan
James C
JC
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000950:Antigens, Ly; D002460:Cell Line; D003001:Cloning, Molecular; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000302:isolation & purification; D019281:Dimerization; D005260:Female; D005816:Genetic Complementation Test; D006239:Haplotypes / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006650:Histocompatibility Testing; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D051381:Rats; D011914:Rats, Inbred BN; D011915:Rats, Inbred BUF; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D018076:DNA, Complementary; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; C110546:TYROBP protein, human; C038353:histocompatibility antigens RT, rat