Limits...
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.

Show MeSH

Related in: MedlinePlus

Defect of IFN-γ production by NK cells from γ−/− mice  upon stimulation with NK1.1 cross-linking. NK cells from γ+/+ (closed  bar) and γ−/− (open bar) mice were stimulated with immobilized (Fab)′2  fragment of anti-NK1.1 mAb or 1 ng/ml IL-12 and IFN-γ produced in  the culture supernatant was measured. Data are presented as mean ± SD  of triplicate culture.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199168&req=5

Figure 4: Defect of IFN-γ production by NK cells from γ−/− mice upon stimulation with NK1.1 cross-linking. NK cells from γ+/+ (closed bar) and γ−/− (open bar) mice were stimulated with immobilized (Fab)′2 fragment of anti-NK1.1 mAb or 1 ng/ml IL-12 and IFN-γ produced in the culture supernatant was measured. Data are presented as mean ± SD of triplicate culture.

Mentions: Recently, we have shown that cross-linking of NKR-P1 on NK cells with anti-NK1.1 mAb induced not only cytotoxicity but also IFN-γ production (10). Thus, we stimulated purified NK cells from γ−/− mice with immobilized F(ab)′2 fragment of anti-NK1.1 mAb in order to avoid the binding of the Ab to Fc receptors, and measured the amount of IFN-γ produced in the culture supernatant. Surprisingly, NK cells from γ−/− mice did not produce IFN-γ at all upon NKR-P1 cross-linking, whereas NK cells from γ+/+ mice produced a large amount (Fig. 4). In contrast, NK cells from both γ−/− and γ+/+ mice produced almost equal amount of IFN-γ upon IL-12 stimulation. This suggests that the defect of IFN-γ production upon NKR-P1 cross-linking by NK cells from γ−/− mice is not due to the inability of IFN-γ production but the signaling defect via 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)

Defect of IFN-γ production by NK cells from γ−/− mice  upon stimulation with NK1.1 cross-linking. NK cells from γ+/+ (closed  bar) and γ−/− (open bar) mice were stimulated with immobilized (Fab)′2  fragment of anti-NK1.1 mAb or 1 ng/ml IL-12 and IFN-γ produced in  the culture supernatant was measured. Data are presented as mean ± SD  of triplicate culture.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199168&req=5

Figure 4: Defect of IFN-γ production by NK cells from γ−/− mice upon stimulation with NK1.1 cross-linking. NK cells from γ+/+ (closed bar) and γ−/− (open bar) mice were stimulated with immobilized (Fab)′2 fragment of anti-NK1.1 mAb or 1 ng/ml IL-12 and IFN-γ produced in the culture supernatant was measured. Data are presented as mean ± SD of triplicate culture.
Mentions: Recently, we have shown that cross-linking of NKR-P1 on NK cells with anti-NK1.1 mAb induced not only cytotoxicity but also IFN-γ production (10). Thus, we stimulated purified NK cells from γ−/− mice with immobilized F(ab)′2 fragment of anti-NK1.1 mAb in order to avoid the binding of the Ab to Fc receptors, and measured the amount of IFN-γ produced in the culture supernatant. Surprisingly, NK cells from γ−/− mice did not produce IFN-γ at all upon NKR-P1 cross-linking, whereas NK cells from γ+/+ mice produced a large amount (Fig. 4). In contrast, NK cells from both γ−/− and γ+/+ mice produced almost equal amount of IFN-γ upon IL-12 stimulation. This suggests that the defect of IFN-γ production upon NKR-P1 cross-linking by NK cells from γ−/− mice is not due to the inability of IFN-γ production but the signaling defect via 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.

Show MeSH
Related in: MedlinePlus