The D0 Ig-like domain plays a central role in the stronger binding of KIR3DL2 to B27 free H chain dimers.

Abstract

We proposed that the killer cell Ig-like receptor KIR3DL2 binding more strongly to HLA-B27 (B27) β2-microglobulin free H chain (FHC) dimers than other HLA-class I molecules regulates lymphocyte function in arthritis and infection. We compared the function of B27 FHC dimers with other class I H chains and identified contact residues in KIR3DL2. B27 FHC dimers interacted functionally with KIR3DL2 on NK and reporter cells more strongly than did other class I FHCs. Mutagenesis identified key residues in the D0 and other Ig-like domains that were shared and distinct from KIR3DL1 for KIR3DL2 binding to B27 and other class I FHCs. We modeled B27 dimer binding to KIR3DL2 and compared experimental mutagenesis data with computational "hot spot" predictions. Modeling predicts that the stronger binding of B27 dimers to KIR3DL2 is mediated by nonsymmetrical complementary contacts of the D0 and D1 domains with the α1, α2, and α3 domains of both B27 H chains. In contrast, the D2 domain primarily contacts residues in the α2 domain of one B27 H chain. These findings provide novel insights about the molecular basis of KIR3DL2 binding to B27 and other ligands and suggest an important role for KIR3DL2-B27 interactions in controlling the function of NK cells in B27(+) individuals.

• Authors: Hiroko Hatano, Jacqueline Shaw, Kaitlin Marquardt, Zhiyong Zhang, Laurent Gauthier, Stephanie Chanteux, Benjamin Rossi, Demin Li, Julie Mitchell, Simon Kollnberger
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 194 Issue 4 Pg. 1591-601 (Feb 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 25582852 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• HLA-B27 Antigen
• KIR3DL2 protein, human
• Receptors, KIR3DL2

Topics

• Cell Line
• Flow Cytometry
• HLA-B27 Antigen (chemistry, immunology)
• Humans
• Immunoprecipitation
• Killer Cells, Natural (immunology)
• Models, Molecular
• Protein Binding (physiology)
• Protein Multimerization
• Protein Structure, Tertiary (physiology)
• Receptors, KIR3DL2 (chemistry, metabolism)