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Divergent Immunoglobulin G Subclass Activity Through Selective Fc Receptor Binding
Falk Nimmerjahn and
Jeffrey V. Ravetch*
Subclasses of immunoglobulin G (IgG) display substantial differencesin their ability to mediate effector responses, contributingto variable activity of antibodies against microbes and tumors.We demonstrate that the mechanism underlying this long-standingobservation of subclass dominance in function is provided bythe differential affinities of IgG subclasses for specific activatingIgG Fc receptors compared with their affinities for the inhibitoryIgG Fc receptor. The significant differences in the ratios ofactivating-to-inhibitory receptor binding predicted the in vivoactivity. We suggest that these highly predictable functionsassigned by Fc binding will be an important consideration inthe design of therapeutic antibodies and vaccines.
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: ravetch{at}rockefeller.edu
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