Recent Progress on Paired Immunoglobulin-Like Receptors

  • Hiromi Kubagawa
  • Ching-Cheng Chen
  • Ikuko Torii
  • Max D. Cooper
  • Kyoko Masuda
  • Yoshimoto Katsura
  • Hiroshi Kawamoto


Almost 10 years ago the Takai and Kubagawa laboratories independently identified the paired immunoglobulin-like receptors (PIRs) in mice based on limited homology with the human Fcα receptor/CD89 (Hayami et al. 1997; Kubagawa et al. 1997). Two PIR isoforms were identified on the basis of their signaling properties as activating (PIR-A) and inhibitory (PIR-B) types. Pir is a multigene family located on the proximal end of mouse chromosome 7 (Kubagawa et al. 1997; Tun et al. 2003; Yamashita et al. 1998a), in a region syntenic with the human chromosome 19q13 where a cluster of structurally related gene families called the leukocyte receptor complex resides. Among these human genes are the closest PIR homologs, the immunoglobulin (Ig)-like transcripts (ILTs) [also called leukocyte Ig-like receptors (LIRs), monocyte/macrophage Ig-like receptors or CD85; see the new LILR nomenclature at] (Arm et al. 1997; Barten et al. 2001; Colonna et al. 1999; Cosman et al. 1999; Long 1999; Martin et al. 2002; Wagtmann et al. 1997). Paired immunoglobulin-like receptor-A and PIR-B are cell surface glycoproteins with very similar extracellular regions (>92% homology) containing six Ig-like domains, but with structurally and functionally distinct transmembrane and cytoplasmic regions (see Fig. 1). There are multiple PIR-A isoforms (>6), each encoded by a different Pira gene. Paired immunoglobulin-like receptor-As associate non-covalently with the Fc receptor common γ chain (FcRγc), a transmembrane signal transducer that contains immunoreceptor tyrosine-based activation motif (ITAM) “D/ExxYxxL/Ix6–8YxxL/I” (single amino acid code, where x represents any amino acid) in the cytoplasmic tail, to form a cell activation complex (Kubagawa et al. 1999a; Maeda et al. 1998b; Ono et al. 1999; Taylor and McVicar 1999).
Fig. 1

Schematic presentation of paired immunoglobulin-like receptor (PIR)-A and PIR-B. Both PIR-A and PIR-B cDNAs encode type I transmembrane proteins consisting of similar extracellular regions with six Ig-like domains, but having distinctive trans-membrane and cytoplasmic regions. The ectodomain has five or six potential sites for N-linked glycosylation (bars with closed circles). The predicted PIR-A has a short cytoplasmic tail and a positively charged arginine (R) residue in the transmembrane segment, which is noncovalently associated with a negatively charged aspartic acid (D) in the transmembrane domain of the disulfi de-linked homodimer of the Fc receptor common γ chain (FcRγc) carrying immunoreceptor tyrosine-based activation motifs (ITAMs). In contrast, the PIR-B protein has a typical uncharged transmembrane region and a long cytoplasmic tail with immunoreceptor tyrosine-based inhibitory motifs (ITIMs).


Major Histocompatibility Complex Class Adult Bone Marrow Lymphoid Progenitor Leukocyte Receptor Complex Surface Plasmon Resonance Assay 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Hiromi Kubagawa
    • 1
  • Ching-Cheng Chen
    • 1
  • Ikuko Torii
    • 1
  • Max D. Cooper
    • 2
  • Kyoko Masuda
    • 3
  • Yoshimoto Katsura
    • 4
  • Hiroshi Kawamoto
    • 3
  1. 1.Division of Developmental and Clinical ImmunologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Howard Hughes Medical InstituteBirminghamUSA
  3. 3.Laboratory for Lymphocyte DevelopmentRIKEN Research Center for Allergy and ImmunologyYokohamaJapan
  4. 4.Division of Cell Regeneration and Transplantation, Advanced Medical Research CenterNihon University School of MedicineTokyoJapan

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