Purified MHC class I molecules inhibit activated NK cells in a cell-free system in vitro.
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.
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
T
T
Kambayashi
J
J
Michaëlsson
L
L
Fahlén
B J
BJ
Chambers
C L
CL
Sentman
K
K
Kärre
H G
HG
Ljunggren
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D002478:Cells, Cultured; D016654:Genes, RAG-1; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000276:immunology; D055630:Receptors, NK Cell Lectin-Like
D000906:Antibodies; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; C527091:Klra3 protein, mouse; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D055630:Receptors, NK Cell Lectin-Like; D007371:Interferon-gamma; D010047:Ovalbumin