2B4 functions as a co-receptor in human NK cell activation

Simona Sivori, Silvia Parolini, Michela Falco, Emanuela Marcenaro, Roberto Biassoni, Cristina Bottino, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticle

Abstract

Natural cytotoxicity receptors (NKp46, NKp44 and NKp30) play a predominant role in human NK cell triggering during natural cytotoxicity. Human 2B4 also induced NK cell activation in redirected killing assays using anti-2B4 monoclonal antibodies (mAb) and murine targets. Since this effect was confined to a fraction of NK cells, this suggested a functional heterogeneity of 2B4 molecules. Here we show that activation via 2B4 in redirected killing against murine targets is strictly dependent upon the engagement of NKp46 by murine ligand(s) on target cells. Thus, NK cell clones expressing high surface density of NKp46 (NKp46(bright)) were triggered by anti-2B4 mAb, whereas NKp46(dull) clones were not although they expressed a comparable surface density of 2B4. mAb-mediated modulation of NKp46 molecules in NKp46(bright) clones had no effect on the expression of 2B4 while it rendered cells unresponsive to anti-2B4 mAb. Finally, anti-2B4 mAb could induce NK cell triggering in NKp46(dull) clones provided that suboptimal doses of anti-NKp44 or anti-CD16 mAb were added to the redirected killing assay. These results indicate that differences in responses do not reflect a functional heterogeneity of 2B4 but rather depend on the co-engagement of triggering receptors.

Original languageEnglish
Pages (from-to)787-793
Number of pages7
JournalEuropean Journal of Immunology
Volume30
Issue number3
DOIs
Publication statusPublished - 2000

Keywords

  • Activating receptor
  • Natural cytotoxicity
  • NK cell

ASJC Scopus subject areas

  • Immunology

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