Intracytoplasmic sequences involved in the biological properties of low-affinity receptors for IgG expressed by murine macrophages.
Murine macrophages express several receptors for the Fc portion of IgG antibodies (Fc gamma R). These are high-affinity Fc gamma RI, which bind monomeric IgG2a, and low-affinity Fc gamma RII and Fc gamma RIII, which bind IgG1, IgG2a and IgG2b immune complexes. Fc gamma Ri and Fc gamma RIII are multichain receptors. They are composed of an IgG-binding alpha subunit, associated with the same FcR gamma subunit that also associates with mast cell high-affinity IgE receptors (Fc epsilon RI). Fc gamma RII are single-chain receptors. They exist as two isoforms, Fc gamma RIIb1 and Fc gamma RIIb2, differing by a 47-amino acid insertion in the intracytoplasmic domain of Fc gamma RIIb1. Using a model of stable transfectants, we analyzed the biological activities triggered by Fc gamma R and, by site-directed mutagenesis, we mapped functional sequences in the intracytoplasmic domains of recombinant Fc gamma R. A single tyrosine-based activation motif (ITAM), in the intracytoplasmic domain of the FcR gamma subunit of Fc gamma RIII and Fc gamma RI, triggers cell activation, endocytosis and phagocytosis. Two distinct motifs, in the intracytoplasmic domain of Fc gamma RIIb2, trigger endocytosis and phagocytosis, respectively. The Fc gamma RIIb1-specific intracytoplasmic insertion mediates capping and down-regulates Fc gamma RII-dependent internalization. A tyrosine-based inhibitory motif (ITIM), in intracytoplasmic sequences common to Fc gamma RIIb1 and Fc gamma RIIb2, was identified as down-regulating ITAM-dependent cell activation. The variety of biological properties of Fc gamma R implies that macrophage responses triggered by IgG antibodies depend on the complex interplay between different Fc gamma R having common ligands that are coexpressed by mouse macrophages.
Daëron
M
M
Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U255, Institut Curie, Paris, France.
D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm; D004705:Endocytosis / Q000502:physiology*; D005091:Exons / Q000235:genetics; D008214:Lymphocytes; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D015394:Molecular Structure; D009154:Mutation; D010587:Phagocytosis / Q000502:physiology*; D011961:Receptors, Fc / Q000235:genetics / Q000502:physiology*; D017452:Receptors, IgG / Q000235:genetics*; D014443:Tyrosine / Q000235:genetics / Q000502:physiology
D011961:Receptors, Fc; D017452:Receptors, IgG; D014443:Tyrosine