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Expression, crystallization and X-ray diffraction analysis of a complex between B7-H6, a tumor cell ligand for the natural cytotoxicity receptor NKp30, and an inhibitory antibody.


ABSTRACT: Natural killer (NK) cells are essential components of the innate immune response to tumors and viral infections. In humans, the activating natural cytotoxicity receptor NKp30 plays a major role in NK cell-mediated tumor cell lysis. NKp30 recognizes the cell-surface protein B7-H6, which is expressed on tumor, but not healthy, cells. A mouse monoclonal antibody (17B1.3) against human B7-H6 has been developed (Kd = 0.2 µM) to investigate NKp30-mediated NK cell activation and to target tumors expressing B7-H6. Surprisingly, 17B1.3 blocks NK cell activation without interfering with the binding of B7-H6 to NKp30. Understanding the inhibitory mechanism of this antibody will require knowing the structure of 17B1.3 bound to B7-H6. The antigen-binding fragment (Fab) of 17B1.3 was expressed by in vitro folding from bacterial inclusion bodies. The extracellular domain of B7-H6 was produced by secretion from baculovirus-infected insect cells. Crystals of the Fab 17B1.3-B7-H6 complex grown by macro-seeding diffracted to 2.5 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 89.6, b = 138.0, c = 171.4 Å, ? = ? = ? = 90°. Comparison of the Fab 17B1.3-B7-H6 structure with the known NKp30-B7-H6 structure will elucidate the inhibitory mechanism of 17B1.3.

SUBMITTER: Xu X 

PROVIDER: S-EPMC4461333 | BioStudies | 2015-01-01T00:00:00Z

SECONDARY ACCESSION(S): 17B1

REPOSITORIES: biostudies

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