Specific engagement of the CD94/NKG2-A killer inhibitory receptor by the HLA-E class Ib molecule induces SHP-1 phosphatase recruitment to tyrosine-phosphorylated NKG2-A: Evidence for receptor function in heterologous transfectants

Marta Carretero, Gabriella Palmieri, Manuel Llano, Valentino Tullio, Angela Santoni, Daniel E. Geraghty, Miguel López-Botet

Research output: Contribution to journalArticle

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Abstract

It has been recently demonstrated that the CD94/NKG2-A killer inhibitory receptor (KIR) specifically recognizes the HLA-E class Ib molecule. Moreover, the apparent CD94-mediated specific recognition of different HLA class Ia allotypes, transfected into the HLA-defective cell line 721.221, indeed depends on their selective ability to concomitantly stabilize the surface expression of endogenous HLA-E molecules, which confer protection against CD94/NKG2-A+ effector cells. In the present study, we show that a selective engagement of the CD94/NKG2-A inhibitory receptor with a specific monoclonal antibody (mAb) (Z199) was sufficient to induce tyrosine phosphorylation of the NKG2-A subunit and SHP-1 recruitment. These early biochemical events, commonly related to negative signaling pathways, were also detected upon the specific interaction of NK cells with an HLA-E+ 721.221 transfectant (.221-AEH), and were prevented by pre-incubation of .221-AEH with an anti-HLA class I mAb. Furthermore, mAb cross-linking of the CD94/NKG2-A receptor, segregated from other NK-associated molecules by transfection into a rat basophilic leukemia cell line (RBL-2H3), promoted tyrosine phosphorylation of NKG2-A and co-precipitation of SHP-1, together with an inhibition of secretory events triggered via FcεRI. Remarkably, interaction of CD94/NKG2-A+ RBL cells with the HLA-E+ .221-AEH transfectant specifically induced a detectable association of SHP-1 with NKG2-A, constituting a more formal evidence for the receptor-HLA class I interaction.

Original languageEnglish
Pages (from-to)1280-1291
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 1998

Fingerprint

Non-Receptor Type 6 Protein Tyrosine Phosphatase
KIR Receptors
Tyrosine
Monoclonal Antibodies
Phosphorylation
Cell Line
Natural Killer Cells
Transfection
Leukemia

Keywords

  • CD94/NKG2-A
  • HLA-E
  • NK cell
  • Tyrosine phosphatase

ASJC Scopus subject areas

  • Immunology

Cite this

Specific engagement of the CD94/NKG2-A killer inhibitory receptor by the HLA-E class Ib molecule induces SHP-1 phosphatase recruitment to tyrosine-phosphorylated NKG2-A : Evidence for receptor function in heterologous transfectants. / Carretero, Marta; Palmieri, Gabriella; Llano, Manuel; Tullio, Valentino; Santoni, Angela; Geraghty, Daniel E.; López-Botet, Miguel.

In: European Journal of Immunology, Vol. 28, No. 4, 04.1998, p. 1280-1291.

Research output: Contribution to journalArticle

Carretero, Marta ; Palmieri, Gabriella ; Llano, Manuel ; Tullio, Valentino ; Santoni, Angela ; Geraghty, Daniel E. ; López-Botet, Miguel. / Specific engagement of the CD94/NKG2-A killer inhibitory receptor by the HLA-E class Ib molecule induces SHP-1 phosphatase recruitment to tyrosine-phosphorylated NKG2-A : Evidence for receptor function in heterologous transfectants. In: European Journal of Immunology. 1998 ; Vol. 28, No. 4. pp. 1280-1291.
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