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.

Abstract: Provided herein are zymogen activating molecules such as zymogen activating peptides, and methods of identifying and using these zymogen activating molecules such as zymogen activating peptides.