OSCAR is an FcRγ-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells

Abstract

We have isolated a novel cell surface molecule, the human homolog of osteoclast-associated receptor (OSCAR). Unlike mouse OSCAR, hOSCAR is widely transcribed in cells of the myeloid lineage. Notably, hOSCAR is expressed on circulating blood monocytes and CD11c ؉ dendritic cells but not on T and B cells. hOSCAR is continually expressed during differentiation of CD14 ؉ monocytes into dendritic cells and maintained after maturation. hOSCAR associates with the FcR␥ as shown by translocation of FcR␥ to the cell surface in presence of hOSCAR and coimmunoprecipitation from transfected cell lines and ex vivo cells. Engagement of hOSCAR with specific mAb leads to Ca 2؉ mobilization and cytokine release, indicators of cellular activation. Endocytosis of the receptor in dendritic cells was observed, followed by passage of the internalized material into Lamp-1 ؉ and HLA-DR ؉ compartments, suggesting a role in antigen uptake and presentation.Dendritic cells were able to stimulate a T-cell clone specific for an epitope of mouse IgG1 after uptake and processing of the hOSCAR-specific antibody, demonstrating the capacity of this receptor to mediate antigen presentation. hOSCAR thus represents a novel class of molecule expressed by dendritic cells involved in the initiation of the immune response.

CD85j (Leukocyte Ig-Like Receptor-1/Ig-Like Transcript 2) Inhibits Human Osteoclast-Associated Receptor-Mediated Activation of Human Dendritic Cells

“…3). LPS, as shown previously (36), yielded the highest level of cytokine production that was not inhibited by coligation of CD85j (data not shown).…”

“…Its association with the ITAM-bearing FcR␥ confers to hOSCAR the capacity to activate myeloid cells as shown by its ability to trigger calcium flux and cytokine release (36). We also showed that hOSCAR ligation induced phenotypic and functional maturation of DCs, elicited cytokine and chemokine secretion, and synergistically amplified the TLR-induced ability of DCs to prime naive T cell proliferation (37).…”

“…We recently described the human osteoclast-associated receptor (hOSCAR), a novel immune receptor associated with the FcR␥ chain (FcR␥) and involved in endocytosis and Ag presentation through the MHC class II pathway in monocyte-derived DCs (mono-DC) (36). Its association with the ITAM-bearing FcR␥ confers to hOSCAR the capacity to activate myeloid cells as shown by its ability to trigger calcium flux and cytokine release (36).…”

“…hOSCAR (36,37) provided the strongest activating signal for DCs and was therefore chosen for all of the experiments. We show that CD85j inhibits intracellular calcium mobilization and cytokine secretion triggered by ligation of hOSCAR.…”

Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

“…A human ortholog of murine OSCAR was identified by Merck et al (9). OSCAR is expressed on cells of myeloid origin, and it signals through the ITAM-harboring adaptor protein FcRg (9,10).…”