Differences in susceptibility to NK cell killing of two cloned sublines derived from a single clone

The ability of natural killer (NK) cells to discriminate between virus infected or tumor cells and their normal counterparts indicates a highly selective recognition, but the exact target structure remains unknown. We have examined two clones of measles virus persistently infected HeLa cells derived from the same parental clone, one of which, HeLa-mss, is highly susceptible to NK killing, (35% specific lysis at 80:1 lymphocyte to target ratio), whilst the other, HeLa-msr, is totally resistant (0.4-2.4% specific lysis). The HeLa-msr cells also failed to inhibit lysis of the HeLa-mss target cells, indicating that HeLa-msr cells did not share the receptor of HeLa-mss for NK cells. The expression of the two measles virus-encoded surface antigens, the hemagglutinin (HA) and fusion (F) proteins on the plasma membrane was examined by immunofluorescent staining and FACS analysis using monoclonal antibodies to the respective proteins. Approximately equivalent amounts of HA and F antigens were found on the cells of the HeLa-msr and HeLa-mss clones. Immunoprecipitation and PAGE analysis also failed to reveal any qualitative differences in the migration patterns or relative proportion of the measles virus proteins between these cell lines. Nevertheless, the in vitro differences in susceptibility of the two cell lines to NK lysis were found to be important in vivo, since HeLa-mss cells failed to grow as tumors in nude mice while HeLa-msr were highly tumorigenic. Thus, NK cells may either recognize very subtle differences in viral encoded polypeptides, possibly point mutations, or alternatively, they may recognize changes in the host cell membrane induced by insertion of certain viral encoded polypeptides.