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- Title
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.
- Authors
Xu, Xiaoping; Li, Yili; Gauthier, Laurent; Chen, Qianming; Vivier, Eric; Mariuzza, Roy A.
- 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 µ M) 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 P212121, with unit-cell parameters a = 89.6, b = 138.0, c = 171.4 Å, α = β = γ = 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.
- Subjects
LIGANDS (Chemistry); IMMUNOGLOBULINS; CRYSTALLIZATION; X-ray diffraction
- Publication
Acta Crystallographica: Section F, Structural Biology Communications, 2015, Vol 71, Issue 6, p697
- ISSN
2053-230X
- Publication type
Article
- DOI
10.1107/S2053230X15006755