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 response s in vivo. To examine the effects of m144 on Nh cytotoxicity in vitro, vari ous cell lines were transfected with wild-type m144 or a chimeric construct in which the cytoplasmic domain of m144 was replaced with green fluorescen ce protein. Burkitt lymphoma line Raji expressed a significant level of m14 4 as determined by anti-m144 mAb binding or the green fluorescence of the f usion protein. The level of m144 expression was relatively low compared wit h that of transfected murine class I MHC Dd. However, m144 on Raji cells pa rtially inhibited antibody-dependent cell-mediated cytotoxicity of IL-2-act ivated 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 c lass I MHC homologue m144 partially inhibits MZ cells by interacting with a novel inhibitory receptor. (C) 1999 Academic Press.