The interaction of IgG with Fc gamma receptors on human neutrophils.

The interaction of IgG with Fc gamma receptors on human PMN was studied by investigating the capacity of IgG and some of its fragments to mediate and inhibit, respectively, binding of immune complexes to these receptors and the subsequent activation of the cells. Fragments included Fab/Fc which is monovalent but contains the complete Fc region, Facb (divalent, C gamma 3 domains removed), Fc, pFc' (a C gamma 3 dimer) and a peptide corresponding to the greater part of one C gamma 2 domain (amino acids 278 through 333) including the carbohydrate side chains. F(ab')2 and Fab served as controls. The results indicate that human IgG interacts with human PMN Fc receptors predominantly through its C gamma 2 domains, while binding of rabbit IgG involves additional sites in C gamma 3. The C gamma 2 binding site on human IgG appears to be located between those for C1 and protein A and to contain lysine residues. For its correct exposure the C gamma 2 domains must be kept in the native conformation, in which both the hinge disulfide bridges and the carbohydrate moieties are involved. A role of the sugars in the actual binding, on the other hand, can be excluded.