2B4 engagement mediates rapid LFA-1 and actin-dependent NK cell adhesion to tumor cells as measured by single cell force spectroscopy

J Immunol. 2011 Mar 1;186(5):2757-64. doi: 10.4049/jimmunol.1002867. Epub 2011 Jan 26.

Abstract

Adhesion to tumor target cells is essential for initiation and execution of cellular cytotoxicity. In this study, we use single cell force spectroscopy to determine the exact biophysical values of the interaction forces between NK cells and tumor cells. We show that engagement of the activating NK cell receptor 2B4 can rapidly mediate an increase in the force necessary to separate NK cells from tumor cells, starting from 1 nN and increasing to 3 nN after only 120 s tumor cell contact. This early adhesion was mediated by the integrin LFA-1 and dependent on the actin cytoskeleton. The ability of NK cells to rapidly adhere to tumor target cells is consistent with their function in innate immune responses. Our data further suggest that a killing decision is already made within 120- 300 s of tumor cell contact, supporting the essential function of cell adhesion during the early phase of cellular cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / physiology*
  • Antibodies, Blocking / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, CD / physiology
  • CD48 Antigen
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cell Communication / immunology
  • Cell Line
  • Cell Line, Tumor
  • Coculture Techniques
  • HeLa Cells
  • Humans
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Microscopy, Atomic Force / instrumentation
  • Microscopy, Atomic Force / methods
  • Microscopy, Electron, Scanning / instrumentation
  • Microscopy, Electron, Scanning / methods
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Immunologic / physiology
  • Signal Transduction / immunology
  • Signaling Lymphocytic Activation Molecule Family
  • Time Factors

Substances

  • Actins
  • Antibodies, Blocking
  • Antigens, CD
  • CD244 protein, human
  • CD48 Antigen
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family