ICAM-2 redistributed by ezrin as a target for killer cells

Nature. 1996 Jul 18;382(6588):265-8. doi: 10.1038/382265a0.


Very little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resistant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resistant cells it is evenly distributed. The cytoskeletal-membrane linker protein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropods formation, redistribution of ICAM-2 and ezrin, and sensitizes target cells to interleukin-2-activated killing. These results reveal a new mechanism of target-cell recognition: cytotoxic cells recognize adhesion molecules that are already present on normal cells, but in diseased cells are concentrated into a biologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interactions in the regulation of ICAM-2-mediated adhesive phenomena.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Antigens, CD / physiology
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules / physiology
  • Cell Line
  • Chromosomes, Human, Pair 6
  • Cytoskeletal Proteins / metabolism
  • Cytotoxicity, Immunologic
  • Humans
  • Hybrid Cells
  • Interleukin-2 / physiology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / physiology
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, CD
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • ICAM2 protein, human
  • Interleukin-2
  • Phosphoproteins
  • ezrin