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Purified MHC class I molecules inhibit activated NK cells in a cell-free system in vitro
T Kambayashi1, J Michaëlsson, L Fahlén
1Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Insights
MHC class I molecules directly inhibit natural killer (NK) cell functions, like interferon-gamma release, without needing other cell interactions. This NK cell inhibition is concentration-dependent and influenced by receptor expression levels.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells use inhibitory receptors to interact with MHC class I molecules.
- The necessity of additional NK cell-target cell interactions for MHC class I-mediated inhibition remains unclear.
Purpose of the Study:
- To determine if purified MHC class I molecules alone can inhibit NK cell function.
- To investigate the role of Ly49 inhibitory receptors in MHC class I-induced NK cell inhibition.
Main Methods:
- Used purified H-2K(b) and H-2D(b) molecules to treat spleen-derived lymphokine-activated killer (LAK) cell cultures.
- Stimulated LAK cells with anti-NK1.1 antibody and measured interferon-gamma (IFN-gamma) release.
- Compared inhibition sensitivity in LAK cells from newborn mice, adult mice, and Ly49C-transgenic mice.
Main Results:
- Purified H-2K(b) and H-2D(b) molecules inhibited IFN-gamma release from LAK cells in a concentration-dependent manner.
- LAK cells with lower levels of MHC class I binding Ly49 receptors were less sensitive to H-2K(b) inhibition.
- LAK cells from Ly49C-transgenic mice showed increased sensitivity to H-2K(b) inhibition compared to controls.
Conclusions:
- MHC class I molecules alone are sufficient to induce inhibition of NK cell effector functions, specifically IFN-gamma release.
- The data suggest that MHC class I-induced NK cell inhibition does not require other cell surface molecules beyond MHC class I itself.
- Ly49 receptor expression levels modulate the sensitivity of NK cells to MHC class I-mediated inhibition.
Abstract:
Natural killer cells have been shown to interact with MHC class I molecules via inhibitory receptors. However, it is not known whether the inhibition induced by MHC class I molecules requires other NK cell-target cell interactions. Thus, we examined whether purified MHC class I molecules alone were able to inhibit NK cell function. Purified H-2K(b) and H-2D(b) molecules inhibited the release of IFN-gamma from spleen (H-2(b))-derived lymphokine-activated killer (LAK) cell cultures stimulated by anti-NK1.1 antibody in a concentration-dependent manner. LAK cells generated from newborn mice that express low levels of MHC class I binding Ly49 inhibitory receptors were significantly less sensitive to inhibition by H-2K(b) compared to LAK cells from adult mice. Furthermore, LAK cells generated from spleen cells of Ly49C-transgenic mice were significantly more sensitive to inhibition by H-2K(b) compared to non-transgenic littermates. Taken together, the data indicate that MHC class I induced inhibition of NK cell mediated effector functions, as assessed by IFN-gamma release after NK1.1 triggering, does not require additional cell surface molecules other than MHC class I.