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Costimulation of multiple NK cell activation receptors by NKG2D.

Authors
  • Ho, Emily L1
  • Carayannopoulos, Leonidas N
  • Poursine-Laurent, Jennifer
  • Kinder, Jeremy
  • Plougastel, Beatrice
  • Smith, Hamish R C
  • Yokoyama, Wayne M
  • 1 Division of Rheumatology/Howard Hughes Medical Institute, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
Type
Published Article
Journal
Journal of immunology (Baltimore, Md. : 1950)
Publication Date
Oct 01, 2002
Volume
169
Issue
7
Pages
3667–3675
Identifiers
PMID: 12244159
Source
Medline
License
Unknown

Abstract

The activation of NK cells is mediated through specific interactions between activation receptors and their respective ligands. Little is known, however, about whether costimulation, which has been well characterized for T cell activation, occurs in NK cells. To study the function of NKG2D, a potential NK costimulatory receptor, we have generated two novel hamster mAbs that recognize mouse NKG2D. FACS analyses demonstrate that mouse NKG2D is expressed on all C57BL/6 IL-2-activated NK (lymphokine-activated killer (LAK)) cells, all splenic and liver NK cells, and approximately 50% of splenic NKT cells. Consistent with limited polymorphism of NKG2D, its sequence is highly conserved, and the anti-NKG2D mAbs react with NK cells from a large number of different mouse strains. In chromium release assays, we show that stimulation of NK cells with anti-NKG2D mAb can redirect lysis. Also, enhanced lysis of transfected tumor targets expressing NKG2D ligand could be inhibited by addition of anti-NKG2D mAb. Interestingly, stimulation of LAK cells via NKG2D alone does not lead to cytokine release. However, stimulation of LAK via both an NK activation receptor (e.g., CD16, NK1.1, or Ly-49D) and NKG2D leads to augmentation of cytokine release compared with stimulation through the activation receptor alone. These results demonstrate that NKG2D has the ability to costimulate multiple NK activation receptors.

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