Reconstituted killer cell inhibitory receptors for major histocompatibility complex class I molecules control mast cell activation induced via immunoreceptor tyrosine-based activation motifs

Mathieu Bléry, Jérome Delon, Alain Trautmann, Anna Cambiaggi, Lucia Olcese, Roberto Biassoni, Lorenzo Moretta, Philippe Chavrier, Alessandro Moretta, Marc Daëron, Eric Vivier

Research output: Contribution to journalArticlepeer-review

Abstract

Natural killer and T cells express at their surface, members of a multigenic family of killer cell inhibitory receptors (KIR) for major histocompatibility complex Class I molecules. KIR engagement leads to the inhibition of natural killer and T cell activation programs. We investigated here the functional reconstitution of KIR in a non-lymphoid cell type. Using stable transfection in the RBL-2H3 mast cell line, we demonstrated that (i) KIR can inhibit signals induced by FcεRIγ or CD3ζ polypeptides that bear immunoreceptor tyrosine-based activation motifs; (ii) two distinct immunoreceptor tyrosine-based inhibition motifs-bearing receptors, i.e. KIR and FcγRIIB, use distinct inhibitory pathways since KIR engagement inhibits the intracellular Ca2+ release from endoplasmic reticulum stores, in contrast to FcγRIIB, which only inhibits extracellular Ca2+ entry; (iii) KIR require co-ligation with an immunoreceptor tyrosine-based activation motif-dependent receptor to mediate their inhibitory function. This latter finding is central to the mechanism by which KIR selectively inhibit only the activatory receptors in close vicinity. Taken together our observations also contribute to define and extend the family of immunoreceptor tyrosine-based inhibition motif-bearing receptors involved in the negative control of cell activation.

Original languageEnglish
Pages (from-to)8989-8996
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number14
DOIs
Publication statusPublished - Apr 4 1997

ASJC Scopus subject areas

  • Biochemistry

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