Murine CD160, Ig-Like Receptor on NK Cells and NKT Cells, Recognizes Classical and Nonclassical MHC Class I and Regulates NK Cell Activation

Abstract

Human and mouse NK cells use different families of receptors to recognize MHC class I (MHC I) on target cells. Although human NK cells express both Ig-like receptors and lectin-like receptors specific for MHC I, all the MHC I-specific receptors identified on mouse NK cells to date are lectin-like receptors, and no Ig-like receptors recognizing MHC I have been identified on mouse NK cells. In this study we report the first MHC I-specific Ig-like receptor on mouse NK cells, namely, murine CD160 (mCD160). The expression of mCD160 is restricted to a subset of NK cells, NK1.1+ T cells, and activated CD8+ T cells. The mCD160-Ig fusion protein binds to rat cell lines transfected with classical and nonclassical mouse MHC I, including CD1d. Furthermore, the level of mCD160 on NK1.1+ T cells is modulated by MHC I of the host. Overexpression of mCD160 in the mouse NK cell line KY-2 inhibits IFN-γ production induced by phorbol ester plus ionomycin, whereas it enhances IFN-γ production induced by NK1.1 cross-linking or incubation with dendritic cells. Cross-linking of mCD160 also inhibits anti-NK1.1-mediated stimulation of KY-2 cells. Anti-mCD160 mAb alone has no effect. Thus, mCD160, the first MHC I-specific Ig-like receptor on mouse NK cells, regulates NK cell activation both positively and negatively, depending on the stimulus.

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

“…sCD160-mediated CTL inhibition is directly related to the MHC-I molecule recognition, as no inhibition of cytotoxic activity was detected in the presence of sCD160 in an anti-CD3 mAb-redirected cytotoxicity assay using the murine mastocytoma cell line P815 as target cells (data not shown). Recently, the ILT-2 (CD85j) and ILT-4 (CD85d) receptors, which recognize a broad range of classical and nonclassical human MHC-I molecules, as murine (44) and human (19) CD160, were found to compete with CD8 for the binding to the ␣3 domain of MHC-I molecules (45). It is therefore possible that sCD160, as membrane-bound ILT-2/CD85j, could function as an inhibitory molecule through its association with the MHC-I molecules.…”

A Dual Role for Talin in NK Cell Cytotoxicity: Activation of LFA-1-Mediated Cell Adhesion and Polarization of NK Cells

“…The cDNA encoding the extracellular domain of H60 was PCR amplified, sequenced, and subcloned into the pIG vector (35). H60-Fc fusion protein was produced and purified as described for CD160-Fc fusion protein (34).…”

“…CD160-Fc fusion protein has been previously described (34). H60 cDNA was generated by RT-PCR using RNA isolated from BALB/c mouse splenocytes, subcloned into pBluescript, and sequenced.…”

“…Control samples corresponding to cells bound to ICAM-1 in the presence of Mn 2ϩ were lysed in the presence of 1 mM MnCl 2 . Immunoprecipitation was conducted as described previously (34).…”

Identification and analysis of the human CD160 promoter: implication of a potential AML-1 binding site in promoter activation

“…[9][10][11] It is mainly expressed as a glycosylphosphatidylinositol-anchored multimer at the surface of circulating cytotoxic T CD8 þ cells and NK cells. 12,13 The engagement of CD160 at the surface of these cells leads to the production of cytokines and the induction of cytotoxic functions. Importantly, CD160 is also expressed after activation of CD4 þ T-lymphocytes 14,15 and endothelial cells 16 where the physiological ligands HVEM and HLA-G molecules induce inhibition of the lymphocyte proliferation and endothelial cell apoptosis, respectively.…”