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Institute of Cell and Molecular Biosciences, The Medical School, Newcastle, United Kingdom
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-
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-
. 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was generously supported by grants from the Biotechnology and Biological Sciences Research Council, U.K.
2 Address correspondence and reprint requests to Dr. Jonathan G. Aust, Institute of Cell and Molecular Biosciences, The Medical School, Newcastle NE2 4HH, U.K. E-mail address: j.g.aust{at}ncl.ac.uk
3 The online version of this article contains supplemental material.
4 Abbreviations used in this paper: β2m, β2-microglobulin; BM, bone marrow; MFI, median fluorescence intensity; HA, hemagglutinin.
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