title: Identification of the Ly49L protein: evidence for activating counterparts to inhibitory Ly49 proteins.
abstract: Previous studies have indicated that NK cells from different strains of inbred mice may express distinct Ly49 repertoires. Screening of NK cells from the CBA/J mouse for inhibitory and activating Ly49s revealed a novel DAP12-associated receptor that was immunoprecipitated with the Ly49G-specific mAb 4D11. Degenerate primers were designed to amplify and clone Ly49 cDNAs from CBA/J NK cells. A novel activating Ly49 cDNA was identified, which bears strong homology to the partially sequenced Ly49l gene found in C57BL/6 mice. Transfection of Ly49l into a DAP12+ cell line and subsequent immunoprecipitation experiments showed that Ly49L is likely the activating Ly49 detected by the 4DD11 antibody in CBA/J NK cells. Antibody-mediated cross-linking of Ly49L induced DAP12 phosphorylation, providing evidence that Ly49L is a functional activating receptor. Comparison of the extracellular domains of Ly49 family members indicates that all known activating members have an inhibitory counterpart with a highly related extracellular region.
authors.affiliation: Laboratory of Experimental Immunology, Division of Basic Sciences, and lntramural Research Support Program, National Cancer Institute-FCRDC, Frederick, Maryland 21702-1201, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Makrigiannis
authors.forename: J
authors.initials: J
authors.lastname: Etzler
authors.forename: R
authors.initials: R
authors.lastname: Winkler-Pickett
authors.forename: A
authors.initials: A
authors.lastname: Mason
authors.forename: J R
authors.initials: JR
authors.lastname: Ortaldo
authors.forename: S K
authors.initials: SK
authors.lastname: Anderson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000950:Antigens, Ly; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D000950:Antigens, Ly; D018076:DNA, Complementary; C120113:Ly-49L antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human