Fcγ receptor transmembrane domains: role in cell surface expression, γ chain interaction, and phagocytosis

• Published in: Blood 2003-06, Vol.101 (11), p.4479-4484
• Main Authors: Kim, Moo-Kyung, Huang, Zhen-Yu, Hwang, Pyoung-Han, Jones, Brian A., Sato, Norihito, Hunter, Sharon, Kim-Han, Tai-Hee, Worth, Randall G., Indik, Zena K., Schreiber, Alan D.
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Organs and cells involved in the immune response
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V101.11.4479

We constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the γ chain–dependent Fcγ receptors FcγRIIIA and FcγRI. FcγR chimeras containing the TM and cytoplasmic (CY) domains of the γ chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcγRIIIA TM were poorly expressed. Receptors containing the FcγRI TM and the γ chain CY but lacking the γ chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a γ chain dimer induced by the γ chain TM is not required for efficient phagocytosis. Cotransfection of FcγRI or FcγRIIIA with the chimera CD8-γ-γ (EC-TM-CY) resulted in FcγR cell surface expression and phagocytosis, whereas CD8-CD8-γ, whose TM does not associate with FcγR, allowed cell surface expression of (but not phagocytosis by) FcγRI. CD8-CD8-γ also did not allow surface expression of FcγRIIIA. Exchanging FcγRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcγRI TM are essential for association of FcγRI with the γ chain and phagocytosis. The data indicate that specific sequences in the FcγRIIIA and FcγRI TMs govern their different interactions with the γ chain in cell surface expression and phagocytosis and that γ chain TM sequences are not required for γ chain–mediated phagocytosis. The data identify a specific region of the FcγRI TM and its asparagine as important for FcγRI cell surface expression in the absence of the γ chain and for distinguishing the FcγRI and FcγRIIIA phenotypes.