Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors.
The NKR-P1 family of C-type lectin-like receptors are expressed on natural killer (NK) cells and NKT cells. We report the cloning and characterization of a cognate ligand for the inhibitory mouse NK receptors (NKR)-P1B and NKR-P1D (CD161b/d). The NKR-P1B/D ligand is osteoclast inhibitory lectin (Ocil), also known as Clr-b, a member of a previously cloned group of C-type lectin-related (Clr) proteins linked to the NKR-P1 receptors in the mouse NK gene complex (NKC). Expression of Ocil/Clr-b on mouse tumor cell lines inhibits NK cell-mediated killing. Inhibition is blocked with a new mAb (4A6) specific for Ocil/Clr-b. By using 4A6 mAb, we demonstrate that Ocil/Clr-b is displayed at high levels on nearly all hematopoietic cells, with the exception of erythrocytes, in a pattern that is similar to that of class I MHC molecules. Remarkably, Ocil/Clr-b is frequently down-regulated on mouse tumor cell lines, indicating a role for this receptor-ligand system in a new form of "missing self-recognition" of tumor cells.
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, 485 Life Sciences Addition, Berkeley, CA 94720, USA. james.carlyle@utoronto.ca
James R
JR
Carlyle
Amanda M
AM
Jamieson
Stephan
S
Gasser
Christopher S
CS
Clingan
Hisashi
H
Arase
David H
DH
Raulet
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018076:DNA, Complementary; C527212:Klrb1b protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C429003:Ocil protein, mouse; D011971:Receptors, Immunologic