Title : Structure of the human activating natural cytotoxicity
receptor NKp30 bound to its tumor cell ligand
B7-H6
Abstract :
- Natural killer (NK) cells are lymphocytes of the in na te i mmune syste m that participate in the eli m ination of tumor cells
- In humans, the activating natural cytotoxicity receptors ( NCRs ) NKp30 , NKp44 , and NKp46 play a major role in NK cell-mediated tumor cell lysis
- NKp30 recognizes B7-H6 , a member of the B7 family which is expressed on tumor, but not healthy, cells
- To understand the basis for tumor surveillance by NCRs , we determined the structure of NKp30 , a member of the CD28 family which includes CTLA-4 and PD-1 , in complex with B7-H6
- The overall organization of the NKp30- B7-H6-activating complex differs considerably fro m those of the CTLA-4-B7 and PD-1- PD-L T cell inhibitory complexes
- Whereas CTLA-4 and PD-1 use only the front β-sheet of their Ig-like domain to bind ligands, NKp30 uses both front and back β-sheets, resulting in engagement of B7-H6 via the side, as well as face , of the β-sandwich
- Moreover, B7-H6 contacts NKp30 through the complementarity-determining region ( CDR )-like loops of its V-like domain in an antibody-like interaction that is not observed for B7 or PD-L
- This first structure of an NCR bound to ligand provides a template for designing molecules to stimulate NKp30-mediated cytolytic activity for tumor immunotherapy