Cloning and characterization of a novel activating Ly49 closely related to Ly49A.
The majority of the known Ly49 family members have been isolated from either C57BL/6 (B6) or BALB/c mice. Interestingly, the anti-Ly49 Ab reactivities observed in 129/J mice are different from those of B6 mice. Furthermore, immunoprecipitation of 129/J NK cell lysates with YE1/32 and YE1/48, Abs specific for the inhibitory Ly49A in B6, resulted in detection of the activation-associated DAP12 molecule. These results indicated a need for a more detailed study of this strain. Therefore, a cloning strategy was devised to isolate Ly49 cDNAs from 129/J mice. An immunoreceptor tyrosine-based inhibitory motif-containing, Ly49D-related clone was discovered that we have named Ly49O, and one immunoreceptor tyrosine-based inhibitory motif-lacking, Ly49A-related clone was discovered that we have named Ly49P. No anti-Ly49 mAb reacted with Ly49O, whereas the molecule encoded by the Ly49P cDNA was found to react with YE1/32 and YE1/48. Ly49P was found to associate with mouse DAP12, and Ab-mediated cross-linking of Ly49P resulted in mouse DAP12 phosphorylation and Ca2+ mobilization, indicating that Ly49P is a competent activation receptor. Ly49P, therefore, represents a novel member of the Ly49 activating receptor subfamily.
Makrigiannis
A P
AP
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
Gosselin
P
P
Mason
L H
LH
Taylor
L S
LS
McVicar
D W
DW
Ortaldo
J R
JR
Anderson
S K
SK
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D000950:Antigens, Ly / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D020013:Calcium Signaling / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D002352:Carrier Proteins; D018076:DNA, Complementary; C527088:Klra1 protein, mouse; C527092:Klra4 protein, mouse; D037181:Lectins, C-Type; C400049:Ly49O receptor; C400050:Ly49P receptor; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; C110546:TYROBP protein, human