The expression and function of the NKRP1 receptor family in C57BL/6 mice.
NKRP1 receptors were discovered more than 20 years ago, but due to a lack of appropriate reagents, our understanding of them has remained limited. Using a novel panel of mAbs that specifically recognize mouse NKRP1A, D, and F molecules, we report here that NKRP1D expression is limited to a subpopulation of NK cells, but in contrast to Ly49 receptors appears to be expressed in a normal codominant manner. NKRP1D(-) and NKRP1D(+) NK cells are functionally distinct, NKRP1D(+) cells showing reduced expression of various Ly49 receptors, elevated expression of CD94/NKG2 receptors, and higher IFN-gamma secretion and cytotoxicity than NKRP1D(-) cells. Furthermore, NKRP1D(+) NK cells were unable to kill transfected cells expressing high levels of Clr-b molecules, but readily killed MHC class-I-deficient blast cells that express only low levels of Clr-b. NKRP1A and NKRP1F were expressed at low levels on all splenic and bone marrow NK cells, but mAb-induced cross-linking of NKRP1A and NKRP1F caused no significant enhancement or inhibition of NK cell cytotoxicity and no detectable production of IFN-gamma. NKRP1A, D, and F expression could not be detected on NKT cells, all of which express NKRP1C, and although some activated T cells expressed NKRP1C and perhaps low levels of NKRP1A, no significant expression of NKRP1D or F could be detected. NKRP1 molecules expressed on NK cells or transfectants were down-regulated by cross-linking with mAbs or cell surface ligands, and using this phenomenon as a functional assay for NKRP1-ligand interaction revealed that NKRP1F can recognize CLR-x.
Aust
Jonathan G
JG
Institute of Cell and Molecular Biosciences, The Medical School, Newcastle, United Kingdom. j.g.aust@ncl.ac.uk
Gays
Frances
F
Mickiewicz
Katarzyna M
KM
Buchanan
Ella
E
Brooks
Colin G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000235:genetics / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D055650:NK Cell Lectin-Like Receptor Subfamily A