The role of zinc in the binding of killer cell Ig-like receptors to class I MHC proteins

The role of zinc in the binding of killer cell Ig-like receptors to class I MHC proteins

Departments of ^*Pathology and ^‡Biochemistry, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, United Kingdom; and ^†Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138

Contributed by Jack L. Strominger

Abstract

The binding of killer cell Ig-like Receptors (KIR) to their Class I MHC ligands was shown previously to be characterized by extremely rapid association and dissociation rate constants. During experiments to investigate the biochemistry of receptor–ligand binding in more detail, the kinetic parameters of the interaction were observed to alter dramatically in the presence of Zn²⁺ but not other divalent cations. The basis of this phenomenon is Zn²⁺-induced multimerization of the KIR molecules as demonstrated by BIAcore, analytical ultracentrifugation, and chemical cross-linking experiments. Zn²⁺-dependent multimerization of KIR may be critical for formation of the clusters of KIR and HLA-C molecules, the “natural killer (NK) cell immune synapse,” observed at the site of contact between the NK cell and target cell.

Footnotes

↵ § To whom reprint requests should be addressed. E-mail: htr20{at}hermes.cam.ac.uk.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041618298.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.041618298
Abbreviations:

NK,

natural killer;

KIR,

killer cell Ig-related receptors;

AUC,

analytical ultracentrifugation;

RU,

resonance units