Nature Biotechnology
16, 1357 - 1360 (1998)
doi:10.1038/4339
Cell surface expression of a human IgC Fc chimera activates macrophages
through Fc receptorsPaul F. Stabila1, Shou C. Wong1, 2, Faith A. Kaplan1
& Weng Tao11
Department of Immunology, CytoTherapeutics, Inc.,
Lincoln, RI 02865. 2
Department of Cell and Molecular Biology, CytoTherapeutics,
Inc., Lincoln, RI 02865.
Correspondence should be addressed to Weng Tao (WTAO@CYTO.COM).applied immunologyantibody designopsonizationphagocytosisAntibody-dependent cell-mediated cytotoxicity plays an important role in
the macrophage-mediated destruction of target cells. While the selectivity
is based on antibody specificity, the lytic attack is triggered by Fc receptor−mediated
respiratory burst. To mimic IgG opsonization, a chimeric antibody-like molecule,
containing human IgG1 Fc, was expressed on the surface of mammalian cells.
The transmembrane domain of the human transferrin receptor was fused in-frame
to the N-terminus of the second and third domains of human IgG1 heavy-chain
constant region. This fusion molecule was designed to take advantage of the
type II membrane anchor property of the transferrin receptor to express the
Fc portion of the molecule in a reverse orientation, such that the Fc portion
projected away from the cell surface. This is in contrast to the conventional
cell surface IgG, which is anchored by a C-terminal type I transmembrane domain.
The cell surface expressed reverse Fc no longer activated complement, but
retained Fc receptor−binding capability and activated superoxide production
by macrophages. This activity was completely blocked by an Fc R I−specific
monoclonal antibody.
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