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Association with FcRgamma is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells.

Arase N, Arase H, Park SY, Ohno H, Ra C, Saito T - J. Exp. Med. (1997)

Bottom Line: In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcRgamma chain which is an essential component of Fc receptors for IgG and IgE.Similarly, NK1.1+ T cells from FcRgamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking.These findings demonstrate that the FcRgamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetics, Center for Biological Science, Chiba University School of Medicine, Chiba 260, Japan.

ABSTRACT
Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-linking of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN-gamma production. However, molecular mechanism of NK cell activation via NKR-P1 is not well elucidated. In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcRgamma chain which is an essential component of Fc receptors for IgG and IgE. The association between FcRgamma and NKR-P1 is independent of Fc receptor complexes. Furthermore, NK cells from FcRgamma-deficient mice did not show cytotoxicity or IFN-gamma production upon NKR-P1 cross-linking. Similarly, NK1.1+ T cells from FcRgamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking. These findings demonstrate that the FcRgamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.

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Activation defect of NK cells from FcRγ-deficient mice  upon NKR-P1 crosslinking is not due to the low level of NKR-P1 expression. (A) NK1.1 expression on NK cells from γ+/+ and γ−/− mice.  NK cells from γ+/+ or γ−/− mice were stained with anti-NK1.1 mAb  (solid line) or control Ab (dotted line). (B) Preparation of NK cell population expressing high (hi) and low (lo) level of NKR-P1 from wild-type  mice. (C) Production of IFN-γ by NK cell population expressing low  NKR-P1 upon stimulation with immobilized anti-NK1.1 mAb. Two  NK cell populations expressing high (NK1.1hi) and low (NK1.1lo) level of  NK1.1 as shown in B from γ+/+ mice and NK cells from γ−/− mice were  stimulated with immobilized (Fab)′2 fragment anti-NK1.1 mAb and IFN-γ  production was measured.
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Figure 7: Activation defect of NK cells from FcRγ-deficient mice upon NKR-P1 crosslinking is not due to the low level of NKR-P1 expression. (A) NK1.1 expression on NK cells from γ+/+ and γ−/− mice. NK cells from γ+/+ or γ−/− mice were stained with anti-NK1.1 mAb (solid line) or control Ab (dotted line). (B) Preparation of NK cell population expressing high (hi) and low (lo) level of NKR-P1 from wild-type mice. (C) Production of IFN-γ by NK cell population expressing low NKR-P1 upon stimulation with immobilized anti-NK1.1 mAb. Two NK cell populations expressing high (NK1.1hi) and low (NK1.1lo) level of NK1.1 as shown in B from γ+/+ mice and NK cells from γ−/− mice were stimulated with immobilized (Fab)′2 fragment anti-NK1.1 mAb and IFN-γ production was measured.

Mentions: The failure of NK cell activation through NKR-P1 in γ−/− mice is likely due to a defect in signaling pathway of the NKR-P1 molecule. However, since the NK1.1 expression on the cell surface of NK cells from γ−/− mice is slightly lower than that of γ+/− and γ+/+ mice, it might be attributed to the low expression of the cell surface NKR-P1. To clarify these possibilities, we prepared two populations of NK cells from normal mice expressing low or high level of NKR-P1 (NKR-P1lo and NKR-P1hi, respectively) by cell sorting. The expression level of NKR-P1 on the NKR-P1lo population was almost identical to that of NK cells from γ−/− mice. (Fig. 7, A and B). Then, we stimulated these NK cell populations with immobilized anti-NK1.1 mAb. NKR-P1lo NK cells from γ+/+ mice produced significant amount of IFN-γ upon NKR-P1 cross-linking, although the amount of IFN-γ was lower than that by NKR-P1hi NK cells (Fig. 7 C). In contrast, NK cells from γ−/− mice did not produce any detectable level of IFN-γ upon NKR-P1 cross-linking. These observations confirm the crucial role of FcRγ in signaling pathway through NKR-P1 for NK activation and also demonstrate that FcRγ is partly involved in the expression of the cell surface NKR-P1.


Association with FcRgamma is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells.

Arase N, Arase H, Park SY, Ohno H, Ra C, Saito T - J. Exp. Med. (1997)

Activation defect of NK cells from FcRγ-deficient mice  upon NKR-P1 crosslinking is not due to the low level of NKR-P1 expression. (A) NK1.1 expression on NK cells from γ+/+ and γ−/− mice.  NK cells from γ+/+ or γ−/− mice were stained with anti-NK1.1 mAb  (solid line) or control Ab (dotted line). (B) Preparation of NK cell population expressing high (hi) and low (lo) level of NKR-P1 from wild-type  mice. (C) Production of IFN-γ by NK cell population expressing low  NKR-P1 upon stimulation with immobilized anti-NK1.1 mAb. Two  NK cell populations expressing high (NK1.1hi) and low (NK1.1lo) level of  NK1.1 as shown in B from γ+/+ mice and NK cells from γ−/− mice were  stimulated with immobilized (Fab)′2 fragment anti-NK1.1 mAb and IFN-γ  production was measured.
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Figure 7: Activation defect of NK cells from FcRγ-deficient mice upon NKR-P1 crosslinking is not due to the low level of NKR-P1 expression. (A) NK1.1 expression on NK cells from γ+/+ and γ−/− mice. NK cells from γ+/+ or γ−/− mice were stained with anti-NK1.1 mAb (solid line) or control Ab (dotted line). (B) Preparation of NK cell population expressing high (hi) and low (lo) level of NKR-P1 from wild-type mice. (C) Production of IFN-γ by NK cell population expressing low NKR-P1 upon stimulation with immobilized anti-NK1.1 mAb. Two NK cell populations expressing high (NK1.1hi) and low (NK1.1lo) level of NK1.1 as shown in B from γ+/+ mice and NK cells from γ−/− mice were stimulated with immobilized (Fab)′2 fragment anti-NK1.1 mAb and IFN-γ production was measured.
Mentions: The failure of NK cell activation through NKR-P1 in γ−/− mice is likely due to a defect in signaling pathway of the NKR-P1 molecule. However, since the NK1.1 expression on the cell surface of NK cells from γ−/− mice is slightly lower than that of γ+/− and γ+/+ mice, it might be attributed to the low expression of the cell surface NKR-P1. To clarify these possibilities, we prepared two populations of NK cells from normal mice expressing low or high level of NKR-P1 (NKR-P1lo and NKR-P1hi, respectively) by cell sorting. The expression level of NKR-P1 on the NKR-P1lo population was almost identical to that of NK cells from γ−/− mice. (Fig. 7, A and B). Then, we stimulated these NK cell populations with immobilized anti-NK1.1 mAb. NKR-P1lo NK cells from γ+/+ mice produced significant amount of IFN-γ upon NKR-P1 cross-linking, although the amount of IFN-γ was lower than that by NKR-P1hi NK cells (Fig. 7 C). In contrast, NK cells from γ−/− mice did not produce any detectable level of IFN-γ upon NKR-P1 cross-linking. These observations confirm the crucial role of FcRγ in signaling pathway through NKR-P1 for NK activation and also demonstrate that FcRγ is partly involved in the expression of the cell surface NKR-P1.

Bottom Line: In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcRgamma chain which is an essential component of Fc receptors for IgG and IgE.Similarly, NK1.1+ T cells from FcRgamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking.These findings demonstrate that the FcRgamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetics, Center for Biological Science, Chiba University School of Medicine, Chiba 260, Japan.

ABSTRACT
Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-linking of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN-gamma production. However, molecular mechanism of NK cell activation via NKR-P1 is not well elucidated. In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcRgamma chain which is an essential component of Fc receptors for IgG and IgE. The association between FcRgamma and NKR-P1 is independent of Fc receptor complexes. Furthermore, NK cells from FcRgamma-deficient mice did not show cytotoxicity or IFN-gamma production upon NKR-P1 cross-linking. Similarly, NK1.1+ T cells from FcRgamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking. These findings demonstrate that the FcRgamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.

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Related in: MedlinePlus