Role of NKG2D in tumor cell lysis mediated by human NK cells: Cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin

Daniela Pende, Claudia Cantoni, Paola Rivera, Massimo Vitale, Roberta Castriconi, Stefania Marcenaro, Marina Nanni, Roberto Biassoni, Cristina Bottino, Alessandro Moretta, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

NKG2D is a recently described activating receptor expressed by both NK cells and CTL. In this study we investigated the role of NKG2D in the natural cytolysis mediated by NK cell clones. The role of NKG2D varied depending on the type of target cells analyzed. Lysis of various tumors appeared to be exclusively natural cytotoxicity receptors (NCR) dependent. In contrast, killing of another group of target cells, including not only the epithelial cell lines HELA and IGROV-1, but also the FO-1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even normal PHA-induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell clones expressing low surface densities of NCR (NCRdull) could lyse these tumors in an exclusively NKG2D-dependent fashion. Remarkably, not all of these targets expressed MICA/B, thus implying the existence of additional ligands recognized by NKG2D, possibly represented by GPI-linked molecules. Finally, we show that the engagement of different HLA class I-specific inhibitory receptors by either specific antibodies or the appropriate HLA class I ligand led to inhibition of NKG2D-mediated NK cell triggering.

Original languageEnglish
Pages (from-to)1076-1086
Number of pages11
JournalEuropean Journal of Immunology
Volume31
Issue number4
DOIs
Publication statusPublished - 2001

Keywords

  • B
  • MICA
  • Natural cytotoxicity receptor
  • Natural killer cell
  • NKG2D
  • Tumor cell lysis

ASJC Scopus subject areas

  • Immunology

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