Inhibition of NK cells by murine CMV-encoded class I MHC homologue m144.
Murine cytomegalovirus (CMV)-encoded protein m144 is homologous to class I MHC heavy-chain and is thought to regulate NK-cell-mediated immune responses in vivo. To examine the effects of m144 on NK cytotoxicity in vitro, various cell lines were transfected with wild-type m144 or a chimeric construct in which the cytoplasmic domain of m144 was replaced with green fluorescence protein. Burkitt lymphoma line Raji expressed a significant level of m144 as determined by anti-m144 mAb binding or the green fluorescence of the fusion protein. The level of m144 expression was relatively low compared with that of transfected murine class I MHC Dd. However, m144 on Raji cells partially inhibited antibody-dependent cell-mediated cytotoxicity of IL-2-activated NK cells. NK cells from the CMV-susceptible BALB/c as well as those from the resistant C57BL/6 mice were inhibited by m144. Antibodies against the known murine NK inhibitory receptors Ly-49A, C, G, and I did not affect the inhibitory effect of m144. These results suggest that the murine CMV class I MHC homologue m144 partially inhibits NK cells by interacting with a novel inhibitory receptor.
Kubota
A
A
Terry Fox Laboratory, British Columbia Cancer Agency, British Columbia, Canada.
Kubota
S
S
Farrell
H E
HE
Davis-Poynter
N
N
Takei
F
F
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000950:Antigens, Ly; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D055630:Receptors, NK Cell Lectin-Like; D011994:Recombinant Proteins / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013764:Tetrahydronaphthalenes; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism