Abstract: The present disclosure relates to non-natural NKG2D receptors attached to mammalian cell surfaces wherein the non-natural receptors do not directly signal or directly activate the cell when the receptor is bound by cognate non-natural ?1-?2 domains of NKG2D ligands modified to specifically bind the non-natural NKG2D receptors. The non-natural ?1-?2 domains of NKG2D ligands may be attached to heterologous atoms or molecules including polypeptides, in some embodiments cytokines or modified cytokines, antibodies or fragments of antibodies.

Abstract: The present disclosure relates to non-natural NKG2D receptors attached to mammalian cell surfaces wherein the non-natural receptors do not directly signal or directly activate the cell when the receptor is bound by cognate non-natural ?1-?2 domains of NKG2D ligands modified to specifically bind the non-natural NKG2D receptors. The non-natural ?1-?2 domains of NKG2D ligands may be attached to heterologous atoms or molecules including polypeptides, in some embodiments cytokines or modified cytokines, antibodies or fragments of antibodies.

Abstract: This present disclosure relates generally to the production of polypeptides comprised of modified ?1-?2 domains of NKG2D ligands which bind specifically to a non-natural ectodomain of a non-natural NKG2D receptor and wherein heterologous molecules are attached to the modified ?1-?2 domains of NKG2D ligands. The present disclosure further relates to modified ?1-?2 domains of NKG2D ligands attached to heterologous molecules including polypeptides, and in some embodiments, antibodies or fragments of antibodies. The present disclosure also relates to modified forms of the NKG2D receptor engineered to provide a combination of enhanced and diminished binding to non-natural and natural versions of NKG2D ligands, respectively.