Activation of Natural Killer Cells and Dendritic Cells upon Recognition of a Novel CD99-like Ligand by Paired Immunoglobulin-like Type 2 Receptor

Abstract

Paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of the immune system. Here, we report a mouse orthologue of the human activating paired immunoglobulin-like type 2 receptor (PILR) β, which was cloned from a cDNA library of natural killer (NK) cells based on its ability to associate with the DAP12 signaling adaptor protein. The activating PILRβ was expressed not only on NK cells but also on dendritic cells and macrophages. Furthermore, we have identified a novel CD99-like molecule as a ligand for the activating PILRβ and inhibitory PILRα receptors. Transcripts of PILR ligand are present in many tissues, including some T cell lines. Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRβ. Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire

“…5 and SI Appendix, Table S5). Members of other NKR families also showed increased expression on fetal blood γδ T cells compared with αβ T cells: natural killer group 2, member D (NKG2D), natural killer cell p30-related protein (NKp30), sphingosine 1-phosphate receptor 5 (S1PR5), killer cell lectin-like receptor subfamily G member 1 (KLRG1), PILRB, NKG2A, CD158a, and CD158b (SI Appendix, Tables S5-S7) (3,(51)(52)(53). Several adapter proteins [DNAX-activation protein 10 (DAP10), DAP12] and signaling molecules, such as phospholipase C, gamma 2 (PLCG2), PI3K, and CD3zeta, described as being associated with NKR signaling, were enriched as well (SI Appendix, Table S6) (54).…”

EpsinR, a target for pyrenocine B, role in endogenous MHC‐II‐restricted antigen presentation

“…Anti-IL4I1 polyclonal antibody serum was generated in rats immunized with Fc chimera proteins that were prepared by fusing C-terminal IL4I1 fragment (amino acid residues 215-630) with the Fc region of human IgG as described [32]. In brief, truncated IL4I1 (IL4I1 644-1890 ) cDNA from C57BL/6 mice were cloned and inserted into the XhoI cloning site of a modified pME18S expression vector that contained a mouse CD150 leader segment and the Fc segment of human IgG 1 , which was kindly provided by Dr. Hisashi Arase of Osaka University, Japan.…”

Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands

“…PILR␣ and -␤ share high similarity in their extracellular domain but contain highly divergent intracellular signaling domains and resulting functions (4,5). PILR␣ is predominantly expressed in cells of the myelomonocytic lineage, including monocytes/macrophages, granulocytes, and dendritic cells (4,6). PILR␣ has two cytoplasmic immunoreceptor tyrosine-based inhibitory motifs that recruit SHP-1 and SHP-2 to trigger an inhibitory signaling cascade such as reduced intracellular calcium mobilization (4,5).…”

“…PILR␣ has two cytoplasmic immunoreceptor tyrosine-based inhibitory motifs that recruit SHP-1 and SHP-2 to trigger an inhibitory signaling cascade such as reduced intracellular calcium mobilization (4,5). PILR␤, however, associates with the immunoreceptor tyrosinebased activation motif-bearing DAP12 adaptor molecule to deliver activating signals (6). Recent evidence suggests that modulation of the PILR pathway, by triggering PILR␣ with an agonist antibody or by deleting PILR␤, attenuates pulmonary inflammation, emphasizing the importance of this pathway in the innate immune response (7).…”

“…PILR␣ ligands identified to date include mouse CD99 (mCD99) (6), PILR-associating neural protein (PANP) (8), and HSV-1 glycoprotein B (HSV-1 gB) (9). CD99 is a single chain glycoprotein that participates in the migration of leukocytes through endothelial junctions by homophilic interaction (10,11).…”