Biochemical Nature and Cellular Distribution of the Paired Immunoglobulin-like Receptors, PIR-A and PIR-B

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  • Hiromi Kubagawa
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Ching-Cheng Chen
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Le Hong Ho
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Toshihide Shimada
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Lanier Gartland
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Charles Mashburn
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Takahiro Uehara
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Jeffrey V. Ravetch
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
  • Max D. Cooper
    From the Division of Developmental and Clinical Immunology, *Department of Pathology, ‡Department of Microbiology, §Department of Pediatrics, and ‖Department of Medicine, University of Alabama at Birmingham, and the ¶Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the **Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021

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<jats:p>PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of ∼85 and ∼120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common γ (FcRγc) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of ∼120 kD, PIR-A transfectants expressed the ∼85-kD molecules exclusively intracellularly; PIR-A and FcRγc cotransfectants expressed the PIR-A/ FcRγc complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRγc−/− mice whereas PIR-A was not. Cell surface levels of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRγc chain association for cell surface PIR-A expression; and suggest that the level of FcRγc chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.</jats:p>

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