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Activation of natural killer cells and dendritic cells upon recognition of a novel CD99-like ligand by paired immunoglobulin-like type 2 receptor.

Shiratori I, Ogasawara K, Saito T, Lanier LL, Arase H - J. Exp. Med. (2004)

Bottom Line: Transcripts of PILR ligand are present in many tissues, including some T cell lines.Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRbeta.Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuoku, 260-8670, Japan.

ABSTRACT
Paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of the immune system. Here, we report a mouse orthologue of the human activating paired immunoglobulin-like type 2 receptor (PILR) beta, which was cloned from a cDNA library of natural killer (NK) cells based on its ability to associate with the DAP12 signaling adaptor protein. The activating PILRbeta was expressed not only on NK cells but also on dendritic cells and macrophages. Furthermore, we have identified a novel CD99-like molecule as a ligand for the activating PILRbeta and inhibitory PILRalpha receptors. Transcripts of PILR ligand are present in many tissues, including some T cell lines. Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRbeta. Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

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Cytotoxicity of NK cells against PILR-L–expressing cells. (A) Cytotoxicity of mouse PILRβ-transfected human NKL (left) or mock-transfected NKL cells (right) against mouse PILR-L–transfected 293T cells (closed circles) or parental 293T cells (open circles) is shown. (B) Cytotoxicity of IL-2 expanded NK cells from wild-type mice (left) or DAP12-deficient mice (right) against PILR-L–transfected Ba/F3 cells (closed circles) or parental Ba/F3 cells (open circles) is shown.
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fig7: Cytotoxicity of NK cells against PILR-L–expressing cells. (A) Cytotoxicity of mouse PILRβ-transfected human NKL (left) or mock-transfected NKL cells (right) against mouse PILR-L–transfected 293T cells (closed circles) or parental 293T cells (open circles) is shown. (B) Cytotoxicity of IL-2 expanded NK cells from wild-type mice (left) or DAP12-deficient mice (right) against PILR-L–transfected Ba/F3 cells (closed circles) or parental Ba/F3 cells (open circles) is shown.

Mentions: To examine the function of mouse PILRβ and PILR-L, we transfected mouse PILRβ into NKL, a human NK cell line, and analyzed cytotoxicity of PILRβ-transfected NKL cells against mouse PILR-L–transfected 293T cells. As shown in Fig. 7 A, mouse PILRβ-transfected NKL cells showed cytotoxicity against PILR-L–transfected 293T, but not against parental 293T cells. Mock-transfected NKL did not show cytotoxicity against PILR-L–transfected or parental 293T cells, indicating that NKL cells do not express endogenous activating receptors that can recognize the mouse PILR-L. In addition, soluble recombinant human PILR-Ig did not bind to cells expressing mouse PILR-L (unpublished data). These data indicate that mouse PILRβ recognizes PILR-L–expressing cells and transduces an activating signal into NK cells. We observed that purified mouse PILRα-Ig and PILRβ-Ig did not block cytotoxicity mediated by mouse PILRβ-expressing NKL cells against PILR-L transfectants, probably due to insufficient affinity of these fusion proteins (unpublished data).


Activation of natural killer cells and dendritic cells upon recognition of a novel CD99-like ligand by paired immunoglobulin-like type 2 receptor.

Shiratori I, Ogasawara K, Saito T, Lanier LL, Arase H - J. Exp. Med. (2004)

Cytotoxicity of NK cells against PILR-L–expressing cells. (A) Cytotoxicity of mouse PILRβ-transfected human NKL (left) or mock-transfected NKL cells (right) against mouse PILR-L–transfected 293T cells (closed circles) or parental 293T cells (open circles) is shown. (B) Cytotoxicity of IL-2 expanded NK cells from wild-type mice (left) or DAP12-deficient mice (right) against PILR-L–transfected Ba/F3 cells (closed circles) or parental Ba/F3 cells (open circles) is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211832&req=5

fig7: Cytotoxicity of NK cells against PILR-L–expressing cells. (A) Cytotoxicity of mouse PILRβ-transfected human NKL (left) or mock-transfected NKL cells (right) against mouse PILR-L–transfected 293T cells (closed circles) or parental 293T cells (open circles) is shown. (B) Cytotoxicity of IL-2 expanded NK cells from wild-type mice (left) or DAP12-deficient mice (right) against PILR-L–transfected Ba/F3 cells (closed circles) or parental Ba/F3 cells (open circles) is shown.
Mentions: To examine the function of mouse PILRβ and PILR-L, we transfected mouse PILRβ into NKL, a human NK cell line, and analyzed cytotoxicity of PILRβ-transfected NKL cells against mouse PILR-L–transfected 293T cells. As shown in Fig. 7 A, mouse PILRβ-transfected NKL cells showed cytotoxicity against PILR-L–transfected 293T, but not against parental 293T cells. Mock-transfected NKL did not show cytotoxicity against PILR-L–transfected or parental 293T cells, indicating that NKL cells do not express endogenous activating receptors that can recognize the mouse PILR-L. In addition, soluble recombinant human PILR-Ig did not bind to cells expressing mouse PILR-L (unpublished data). These data indicate that mouse PILRβ recognizes PILR-L–expressing cells and transduces an activating signal into NK cells. We observed that purified mouse PILRα-Ig and PILRβ-Ig did not block cytotoxicity mediated by mouse PILRβ-expressing NKL cells against PILR-L transfectants, probably due to insufficient affinity of these fusion proteins (unpublished data).

Bottom Line: Transcripts of PILR ligand are present in many tissues, including some T cell lines.Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRbeta.Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuoku, 260-8670, Japan.

ABSTRACT
Paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of the immune system. Here, we report a mouse orthologue of the human activating paired immunoglobulin-like type 2 receptor (PILR) beta, which was cloned from a cDNA library of natural killer (NK) cells based on its ability to associate with the DAP12 signaling adaptor protein. The activating PILRbeta was expressed not only on NK cells but also on dendritic cells and macrophages. Furthermore, we have identified a novel CD99-like molecule as a ligand for the activating PILRbeta and inhibitory PILRalpha receptors. Transcripts of PILR ligand are present in many tissues, including some T cell lines. Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRbeta. Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

Show MeSH