Characterization and molecular cloning of rat C1qRp, a receptor on NK cells

Abstract

Here we report the generation of monoclonal antibodies (mAb) LOV3 and LOV8 to a 110–130‐kDa membrane glycoprotein expressed by rat NK cells. This NK surface molecule was identified by eucaryotic expression cloning as the structural orthologue of the phagocytosis‐stimulating receptor for complement factor C1q and mannose‐binding lectin on human macrophages, C1qRp. Rat C1qRp is a monomeric type I integral membrane protein consisting of 643 amino acids with an N‐terminal lectin–like domain, five epidermal growth factor–like domains, a transmembrane domain and a 45‐residue cytoplasmic domain. It is encoded by a single gene on rat chromosome 3q41‐q42 and is 67% and 87.5% identical at the amino acid level to human and mouse C1qRp, respectively. Rat C1qRp is expressed by resting and by activated NK cells, on subpopulations of NKR‐P1+ T cells (NK/T cells), dendritic cells, macrophages and granulocytes, but not by B cells or NKR‐P1– T cells. Expression of this innate immune receptor is therefore not restricted to hematopoietic cells of the myeloid lineage, but is also expressed on subsets of cells of lymphoid origin. The mAb did not affect the cytotoxic function of NK cells, and C1qRp on NK cells may have functions not related to NK killing.

Human C1qRp Is Identical with CD93 and the mNI-11 Antigen But Does Not Bind C1q

“…4f). Occasional colocalization of CD11c with C1qRp was observed and may represent dendritic cells that have been shown to express C1qRp in the rat (25). Similar experiments in which the anti-C1qRp mAb BIIG-4 was used in combination with polyclonal rabbit anti-␣-1-antichymotrypsin, a monocyte/macrophage marker (26,27), confirmed the absence of C1qRp on macrophages.…”

Rat NKp46 activates natural killer cell cytotoxicity and is associated with FcɛRIγ and CD3ζ

“…3A). As previously shown, a subpopulation of rat CD3 ϩ cells is NKR-P1 dim [35]. The functional nature of this cell population is poorly investigated, and they may represent NKT cells or conventional T cells expressing NK cell markers.…”

Soluble CD93 Induces Differentiation of Monocytes and Enhances TLR Responses

“…CD93 consists of a signal peptide, a C-type carbohydrate-recognition domain (CRD), five epidermal growth factor (EGF)-like domains, a mucin domain, a single transmembrane domain, and an intracellular domain with a potential tyrosine kinase phosphorylation site (2,(4)(5)(6)(7)(8). CD93 homologs in mouse and rat are known as AA4 and are 67-87% identical (rat versus mouse: 87%; human versus mouse: 67%; human versus rat: 77%) to the human isoform (9)(10)(11)(12). Expression of CD93 occurs in various cell types including myeloid cells, hematopoietic stem cells, NK cells, platelets, microglia, and endothelial cells, but not in tissue macrophages (2,(12)(13)(14)(15)(16).…”

“…CD93 homologs in mouse and rat are known as AA4 and are 67-87% identical (rat versus mouse: 87%; human versus mouse: 67%; human versus rat: 77%) to the human isoform (9)(10)(11)(12). Expression of CD93 occurs in various cell types including myeloid cells, hematopoietic stem cells, NK cells, platelets, microglia, and endothelial cells, but not in tissue macrophages (2,(12)(13)(14)(15)(16).…”