Molecular Cloning of a Novel Murine Cell-surface Glycoprotein Homologous to Killer Cell Inhibitory Receptors

Abstract

We have isolated a cDNA clone encoding a novel murine cell-surface glycoprotein. This polypeptide is predicted to be composed of a signal peptide of 23 amino acids, an extracellular region of 620 amino acids that contains six immunoglobulin-like domains with five potential N-glycosylation sites, a transmembrane sequence of 20 amino acids, and a cytoplasmic tail of 178 amino acids with four sets of sequences similar to the immunoreceptor tyrosine-based inhibition motif. The relative molecular mass of the mature polypeptide is calculated to be 90,520 Da. The polypeptide, designated as p91, shows striking homologies to human killer cell inhibitory receptors, a murine gp49B1 protein, a bovine Fc␥2 receptor, and a human Fc␣ receptor. The mRNA of p91 was especially abundant in murine macrophages. Western blot analysis using p91-specific anti-peptide sera detected a 130-kDa polypeptide in macrophages. Surface biotinylation and immunoprecipitation analysis verified the surface expression of the translation products on COS-1 cells transfected with the p91 cDNA, but the cells failed to show any Fc binding activity.

Paired Ig-Like Receptors Bind to Bacteria and Shape TLR-Mediated Cytokine Production

“…All of the ectodomains, each containing six Ig-like domains, are Ͼ92% identical at the amino acid level (20,21). Therefore, it had been thought that both PIR-B and PIR-A recognize the same ligands.…”

“…The fact that PIR-B has ITIMs in the cytoplasmic region (20,21) suggests that PIR-B does transmit an inhibitory signal in macrophages upon microbial recognition. We demonstrate in this study that upon binding to S. aureus, PIR-B suppresses the TLR-mediated inflammatory response via the anti-inflammatory cytokine IL-10.…”

“…The ectodomain of PIR-A shares Ͼ92% aa identity with that of PIR-B (20,21). This result prompted us to investigate whether PIR-A could also bind S. aureus.…”

A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells

“…Further genomic studies are necessary to establish whether all of the cloned ILT5 variants are encoded by different alleles at the same locus or by different loci. Human ILT receptors are homologous to murine paired Ig-like receptors (PIRs) [21,27,28] and murine gp49 receptors [29][30][31][32][33]. PIRs are members of the Ig-superfamily characterized by six extracellular Ig-SF domains and by differing transmembrane and cytoplasmic domains.…”

Eosinophils unleashed

“…1 This suggests that it may be important to identify therapeutic strategies that specifically target LSCs while maintaining normal hematopoietic stem cells (HSCs). Previously, Guzman et al reported the activity of a natural compound, parthenolide (PTL), as a potent in vitro agent that selectively affects leukemic initiating cells but not normal progenitors.…”