Recognition and killing of human and murine pancreatic β cells by the NK receptor NKp46

Chamutal Gur, Jonatan Enk, Sameer A. Kassem, Yaron Suissa, Judith Magenheim, Miri Stolovich-Rain, Tomer Nir, Hagit Achdout, Benjamin Glaser, James Shapiro, Yaakov Naparstek, Angel Porgador, Yuval Dor, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Type 1 diabetes is an incurable disease that is currently treated by insulin injections or in rare cases by islet transplantation.We have recently shown that NKp46, a major killer receptor expressed by NK cells, recognizes an unknown ligand expressed by β cells and that in the absence of NKp46, or when its activity is blocked, diabetes development is inhibited. In this study, we investigate whether NKp46 is involved in the killing of human β cells that are intended to be used for transplantation, and we also thoroughly characterize the interaction between NKp46 and its human and mouse β cell ligands. We show that human β cells express an unknown ligand for NKp46 and are killed in an NKp46-dependent manner. We further demonstrate that the expression of the NKp46 ligand is detected on human β cells already at the embryonic stage and that it appears on murine β cells only following birth. Because the NKp46 ligand is detected on healthy β cells, we wondered why type 1 diabetes does not develop in all individuals and show that NK cells are absent from the vicinity of islets of healthy mice and are detected in situ in proximity with β cells in NOD mice. We also investigate the molecular mechanisms controlling NKp46 interactions with its β cell ligand and demonstrate that the recognition is confined to the membrane proximal domain and stalk region of NKp46 and that two glycosylated residues of NKp46, Thr 125 and Asn216, are critical for this recognition.

Original languageEnglish
Pages (from-to)3096-3103
Number of pages8
JournalJournal of Immunology
Issue number6
StatePublished - 15 Sep 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Recognition and killing of human and murine pancreatic β cells by the NK receptor NKp46'. Together they form a unique fingerprint.

Cite this