Human CD300C Delivers an Fc Receptor-γ-dependent Activating Signal in Mast Cells and Monocytes and Differs from CD300A in Ligand Recognition

CD300C is highly homologous with an inhibitory receptor CD300A in an immunoglobulin-like domain among the human CD300 family of paired immune receptors. To clarify the precise expression and function of CD300C, we generated antibodies discriminating between CD300A and CD300C, which recognized a uniq...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of biological chemistry 2013-03, Vol.288 (11), p.7662-7675
Hauptverfasser: Takahashi, Mariko, Izawa, Kumi, Kashiwakura, Jun-ichi, Yamanishi, Yoshinori, Enomoto, Yutaka, Kaitani, Ayako, Maehara, Akie, Isobe, Masamichi, Ito, Shinichi, Matsukawa, Toshihiro, Nakahara, Fumio, Oki, Toshihiko, Kajikawa, Masunori, Ra, Chisei, Okayama, Yoshimichi, Kitamura, Toshio, Kitaura, Jiro
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:CD300C is highly homologous with an inhibitory receptor CD300A in an immunoglobulin-like domain among the human CD300 family of paired immune receptors. To clarify the precise expression and function of CD300C, we generated antibodies discriminating between CD300A and CD300C, which recognized a unique epitope involving amino acid residues CD300A(F56-L57) and CD300C(L63-R64). Notably, CD300C was highly expressed in human monocytes and mast cells. Cross-linking of CD300C by its specific antibody caused cytokine/chemokine production of human monocytes and mast cells. Fc receptor γ was indispensable for both efficient surface expression and activating functions of CD300C. To identify a ligand for CD300A or CD300C, we used reporter cell lines expressing a chimera receptor harboring extracellular CD300A or CD300C and intracellular CD3ζ, in which its unknown ligand induced GFP expression. Our results indicated that phosphatidylethanolamine (PE) among the lipids tested and apoptotic cells were possible ligands for both CD300C and CD300A. PE and apoptotic cells more strongly induced GFP expression in the reporter cells through binding to extracellular CD300A as compared with CD300C. Differential recognition of PE by extracellular CD300A and CD300C depended on different amino acid residues CD300A(F56-L57) and CD300C(L63-R64). Interestingly, GFP expression induced by extracellular CD300C-PE binding in the reporter cells was dampened by co-expression of full-length CD300A, indicating the predominance of CD300A over CD300C in PE recognition/signaling. PE consistently failed to stimulate cytokine production in monocytes expressing CD300C with CD300A. In conclusion, specific engagement of CD300C led to Fc receptor γ-dependent activation of mast cells and monocytes. Background: Human CD300C is not fully characterized because of the unavailability of its specific antibody. Results: Stimulation with a specific CD300C antibody activates human monocytes and mast cells that express high levels of CD300C. Conclusion: Specific engagement of CD300C, but not its co-engagement with CD300A, delivers an Fc receptor-γ-dependent activating signal. Significance: The activating function of CD300C is associated with its ligand specificity.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.434746