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Expression of ligands for activating natural killer cell receptors on cell lines commonly used to assess natural

Alexandra Tremblay-McLean1,2, Sita Coenraads1, Zahra Kiani1,2

  • 1Research Institute of the McGill University Health Center, Glen Site, 1001 Décarie Boulevard, Block E, Rm EM3.3238, Montréal, Québec, H4A 3J1, Canada.

BMC Immunology
|January 31, 2019
PubMed
Abstract

Insights

Natural killer (NK) cell activation depends on activating receptor ligands. Differences in these ligands on K562, 721.221, and CEM.NKr.CCR5 cells explain varied NK cell responses and cytotoxicity.

Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • Natural killer (NK) cell responses are regulated by inhibitory and activating receptors.
  • Human Leukocyte Antigen (HLA) null cells and CEM.NKr.CCR5 cells are used to study NK cell activation via missing-self and antibody-dependent mechanisms, respectively.
  • K562 and 721.221 cell lines lack inhibitory NK cell receptor ligands, prompting investigation into activating ligand expression.

Purpose of the Study:

  • To investigate if differences in activating natural killer cell receptor ligand expression explain varied NK cell functional responses to K562, 721.221, and CEM.NKr.CCR5 cells.
  • To correlate ligand expression with NK cell activation, cytotoxicity, and cytokine secretion.

Main Methods:

  • Comparative analysis of activating NK cell receptor ligand expression on K562, 721.221, and CEM.NKr.CCR5 cell lines using flow cytometry.
  • Assessment of NK cell functional subsets and degranulation (CD107a) following stimulation with these cell lines.

Main Results:

  • K562 cells showed higher intensity of ligands for NK G2D and Natural Cytotoxicity Receptors.
  • 721.221 cells expressed a greater number of ligands for activating receptors, including CD48, CD80, and CD86, at higher intensities.
  • CEM.NKr.CCR5 cells expressed high levels of CD48 and ICAM-2, but fewer ligands for other activating receptors.

Conclusions:

  • Ligands on K562 cells induce NK cell-mediated cytolysis, evidenced by CD107a function.
  • The diverse ligands on 721.221 cells activate a broader range of NK cell functions, including cytokine secretion.
  • Limited activating ligands on CEM.NKr.CCR5 cells contribute to their resistance to antibody-independent NK cell killing.
Keywords:
721.221Activating NK receptor ligandsCEM.NKr.CCR5HLA null cellsK562NK cells

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