Divergent immunoglobulin g subclass activity through selective Fc receptor binding

F Nimmerjahn, JV Ravetch - Science, 2005 - science.org
Science, 2005science.org
Subclasses of immunoglobulin G (IgG) display substantial differences in their ability to
mediate effector responses, contributing to variable activity of antibodies against microbes
and tumors. We demonstrate that the mechanism underlying this long-standing observation
of subclass dominance in function is provided by the differential affinities of IgG subclasses
for specific activating IgG Fc receptors compared with their affinities for the inhibitory IgG Fc
receptor. The significant differences in the ratios of activating-to-inhibitory receptor binding …
Subclasses of immunoglobulin G (IgG) display substantial differences in their ability to mediate effector responses, contributing to variable activity of antibodies against microbes and tumors. We demonstrate that the mechanism underlying this long-standing observation of subclass dominance in function is provided by the differential affinities of IgG subclasses for specific activating IgG Fc receptors compared with their affinities for the inhibitory IgG Fc receptor. The significant differences in the ratios of activating-to-inhibitory receptor binding predicted the in vivo activity. We suggest that these highly predictable functions assigned by Fc binding will be an important consideration in the design of therapeutic antibodies and vaccines.
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