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Identification of a cellular ligand for the natural cytotoxicity receptor NKp44

Florence Baychelier1, Alexis Sennepin, Myriam Ermonval

  • 1Laboratoire Immunité et Infection, Institut National de la Santé et de la Recherche Médicale, UMR-S945.

Blood
|August 21, 2013
PubMed

Insights

Researchers discovered NKp44L, a novel protein isoform, as a ligand for natural killer (NK) cell receptor NKp44. This molecule acts as a danger signal, crucial for NK cell-mediated immunity against tumors.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity, eliminating infected and tumor cells.
  • NK cells utilize activating and inhibitory receptors to identify targets.
  • NKp44 is an activating receptor exclusively found on activated NK cells.

Purpose of the Study:

  • To identify the cellular ligand for the NK cell receptor NKp44.
  • To characterize the novel ligand's function and cellular distribution.
  • To elucidate its role in NK cell-mediated cytotoxicity and innate immunity.

Main Methods:

  • Identification of NKp44L as a novel isoform of the mixed-lineage leukemia-5 (MLL5) protein.
  • Analysis of NKp44L subcellular localization, particularly its cell-surface expression.
  • Assessment of NK cell lysis activity upon blockade with anti-NKp44L antibodies.

Main Results:

  • NKp44L, a cell-surface expressed MLL5 isoform, binds to the NKp44 receptor.
  • NKp44L is absent in healthy individuals but present on various tumor and transformed cells.
  • Antibodies targeting NKp44L significantly reduce NK cell-mediated cytotoxicity.

Conclusions:

  • NKp44L is a critical cellular ligand for NKp44, playing a key role in NK cell-mediated innate immunity.
  • The expression of NKp44L on tumor cells serves as a danger signal, activating the NK cell network.
  • NKp44L represents a potential therapeutic target for enhancing anti-tumor immunity.

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