Ly‐49‐independent inhibition of natural killer cell‐mediated cytotoxicity by a soluble major histocompatibility complex class I molecule

Claude Roth*, Philippe Kourilsky, David M. Ojcius

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations


Natural killer (NK) cells lyse their targets in a non‐major histocompatibility complex (MHC)‐restricted manner, and the cytotoxicity can be inhibited by a number of MHC class I allele products, suggesting that NK cells may have a “positive receptor” that recognizes the target and a “negative receptort” that receives an inhibitory signal from class I. Since negative receptors could also exert their effect by masking a positive ligand, we have determined whether there may be a direct interaction between class I and an NK surface receptor by measuring cytotoxicity in the presence of a soluble class I molecule, Kd. Soluble Kd at micromolar concentrations could efficiently block NK cell cytotoxicity, suggesting that class I has a direct effect on cytotoxicity, rather than masking another target cell ligand. Inhibition required that Kd be at least divalent, probably because of its higher affinity or its ability to cross‐link the NK surface receptor. In addition, the effect was independent of the peptide used to load Kd, and there was inhibition of cytotoxicity of NK cells derived from either H‐2d or H‐2b mice. Finally, depletion of NK cells expressing Ly‐49 had no effect on the specific inhibition by Kd, raising the possibility that NK cells are endowed with additional negative receptors besides Ly‐49. Taken together, these results suggest that there may be a family of NK receptors recognizing different class I alleles, which can receive negative signals by directly binding to class I on the target cell surface.

Original languageEnglish
Pages (from-to)2110-2114
Number of pages5
JournalEuropean Journal of Immunology
Issue number9
StatePublished - 09 1994
Externally publishedYes


  • Cytotoxicity
  • Ly‐49
  • Major histocompatibility complex
  • Natural killer cell
  • p58


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