Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family

J Immunol. 2001 Nov 15;167(10):5517-21. doi: 10.4049/jimmunol.167.10.5517.

Abstract

Some CD2 family receptors stimulate NK cell-mediated cytotoxicity through a signaling pathway, which is dependent on the recruitment of an adapter protein called SLAM-associated protein (SAP). In this work we identify a novel leukocyte cell surface receptor of the CD2 family called CD2-like receptor activating cytotoxic cells (CRACC). CRACC is expressed on cytotoxic lymphocytes, activated B cells, and mature dendritic cells, and activates NK cell-mediated cytotoxicity. Remarkably, although CRACC displays cytoplasmic motifs similar to those recruiting SAP, CRACC-mediated cytotoxicity occurs in the absence of SAP and requires activation of extracellular signal-regulated kinases-1/2. Thus, CRACC is a unique CD2-like receptor which mediates NK cell activation through a SAP-independent extracellular signal-regulated kinase-mediated pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • B-Lymphocytes / immunology
  • CD2 Antigens / genetics*
  • Carrier Proteins / physiology
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Lymphoproliferative Disorders / immunology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Immunologic*
  • Sequence Homology, Amino Acid
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • CD2 Antigens
  • Carrier Proteins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • SH2D1A protein, human
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family
  • Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/AA554342
  • GENBANK/AA765813
  • GENBANK/AA921765
  • GENBANK/AI422743
  • GENBANK/H73135