Identification and molecular characterization of a natural mutant of the p50.2/KIR2DS2 activating NK receptor that fails to mediate NK cell triggering

Cristina Bottino, Michela Falco, Simona Sivori, Lorenzo Moretta, Alessandro Moretta, Roberto Biassoni

Research output: Contribution to journalArticle

Abstract

P50/KIR2DS molecules represent the activating form of the HLA-C-specific inhibitory NK receptors. They are characterized, in the transmembrane portion, by a charged amino acid that is involved in coupling with signal-transducing adaptor polypeptides. In this study we identified a novel p50.2/KIR2DS2 surface molecule, isolated from NK cell clones derived from an otherwise normal donor, that was unable to transduce activating signals. Sequence analysis of the cDNA encoding this molecule revealed six non-conservative codon mutations in the exon coding for the putative transmembrane portion. Notably, one of such mutations involved the charged residue lysine thought to be important for the association with signal-transducing polypeptides. Indeed, co-transfection experiments revealed that this naturally occurring p50.2/KIR2DS2 mutant, termed Mp50.2, displayed a sharply reduced ability to associate with DAP12 polypeptides. These data provide the first in vivo demonstration of the crucial role played by the transmembrane region of p50.2 receptor molecules in the functional association with DAP12 adaptor molecules and in the process of activation of NK-mediated cytotoxicity.

Original languageEnglish
Pages (from-to)3569-3574
Number of pages6
JournalEuropean Journal of Immunology
Volume30
Issue number12
DOIs
Publication statusPublished - 2000

Keywords

  • Activating receptors
  • cDNA
  • Killer Ig-like receptor
  • NK cell

ASJC Scopus subject areas

  • Immunology

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