Adhesion to target cells is disrupted by the killer cell inhibitory receptor

Curr Biol. 2000 Jun 29;10(13):777-80. doi: 10.1016/s0960-9822(00)00568-6.

Abstract

Killer cell immunoglobulin-like receptors (KIR) inhibit the cytotoxic activity of natural killer (NK) cells by recruitment of the tyrosine phosphatase SHP-1 to immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in the KIR cytoplasmic tail [1]. The precise steps in the NK activation pathway that are inhibited by KIR are yet to be defined. Here, we have studied whether the initial step of adhesion molecule LFA-1-dependent adhesion to target cells was altered by the inhibitory signal. Using stable expression of an HLA-C-specific KIR in the NK cell line YTS [2] and a two-color flow cytometry assay for conjugate formation, we show that adhesion to a target cell expressing cognate HLA-C was disrupted by KIR engagement. Conjugate formation was abruptly interrupted by KIR within less than 5 minutes. Inhibition of adhesion to target cells was mediated by a chimeric KIR molecule carrying catalytically active SHP-1 in place of its cytoplasmic tail. These results suggest that other ITIM-bearing receptors, many of which have no known function, may regulate adhesion in a wide variety of cell types.

MeSH terms

  • Abatacept
  • Antibodies / pharmacology
  • Antigens, CD
  • Antigens, Differentiation / pharmacology
  • CD28 Antigens / immunology
  • CD28 Antigens / physiology
  • CTLA-4 Antigen
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression
  • HLA-C Antigens / genetics
  • HLA-C Antigens / physiology
  • Humans
  • Immunoconjugates*
  • Intracellular Signaling Peptides and Proteins
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / physiology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / physiology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Receptors, KIR
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HLA-C Antigens
  • HLA-C*02 antigen
  • HLA-C*03 antigen
  • Immunoconjugates
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Immunologic
  • Receptors, KIR
  • Recombinant Fusion Proteins
  • Abatacept
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases