The natural killer cell receptor NKp30 and its cancer cell ligand B7H6

Natural killer (NK) cells recognize and kill cancer cells and virus infected cells through the actions of activating receptors. One such receptor is NKp30 which binds to the cancer cell ligand B7H6. Other ligands have also been proposed. We have shown that the interaction between NKp30 and B7H6 is conserved in two distantly related species, rat and cattle. We have also confirmed that B7H6 is the ligand of most physiological relevance for NKp30 in human cancer cell lines. As B7H6 seems to be solely expressed by cancer cells, it is a potent target for immunotherapy. However, certain cancer cell lines downregulate B7H6 to escape detection by NKp30. We have investigated the mechanisms cell lines use to prevent expression of B7H6 and found that this occurs at several levels, including DNA methylation and also posttranscriptional regulation. Lastly, NKp30 is expressed as different splice variants. We have characterized the unusual intra-exonic splicing of the immunoglobulin domain, showing that the splice signals are conserved in many species, and that the splicing event seems to be cell-specific