Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition

Gautham R. Balaji, Oscar A. Aguilar, Miho Tanaka, Miguel A. Shingu-Vazquez, Zhihui Fu, Benjamin S. Gully, Lewis L. Lanier, James R. Carlyle, Jamie Rossjohn, Richard Berry

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The interaction between natural killer (NK) cell inhibitory receptors and their cognate ligands constitutes a key mechanism by which healthy tissues are protected from NK cell-mediated lysis. However, self-ligand recognition remains poorly understood within the prototypical NKR-P1 receptor family. Here we report the structure of the inhibitory NKR-P1B receptor bound to its cognate host ligand, Clr-b. NKR-P1B and Clr-b interact via a head-to-head docking mode through an interface that includes a large array of polar interactions. NKR-P1B:Clr-b recognition is extremely sensitive to mutations at the heterodimeric interface, with most mutations severely impacting both Clr-b binding and NKR-P1B receptor function to implicate a low affinity interaction. Within the structure, two NKR-P1B:Clr-b complexes are cross-linked by a non-classic NKR-P1B homodimer, and the disruption of homodimer formation abrogates Clr-b recognition. These data provide an insight into a fundamental missing-self recognition system and suggest an avidity-based mechanism underpins NKR-P1B receptor function.

Original languageEnglish
Article number4623
Number of pages12
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 5 Nov 2018

Keywords

  • autoimmunity
  • innate lymphoid cells
  • signal transduction
  • x-ray crystallography

Cite this

Balaji, Gautham R. ; Aguilar, Oscar A. ; Tanaka, Miho ; Shingu-Vazquez, Miguel A. ; Fu, Zhihui ; Gully, Benjamin S. ; Lanier, Lewis L. ; Carlyle, James R. ; Rossjohn, Jamie ; Berry, Richard. / Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition. / Balaji, Gautham R.; Aguilar, Oscar A.; Tanaka, Miho; Shingu-Vazquez, Miguel A.; Fu, Zhihui; Gully, Benjamin S.; Lanier, Lewis L.; Carlyle, James R.; Rossjohn, Jamie; Berry, Richard.

In: Nature Communications, Vol. 9, No. 1, 4623, 05.11.2018.

Research output: Contribution to journalArticleResearchpeer-review

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