IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation

被引:261
作者
Jefferis, R [1 ]
Lund, J [1 ]
Pound, JD [1 ]
机构
[1] Univ Birmingham, Sch Med, Dept Immunol, Birmingham B15 2TT, W Midlands, England
关键词
D O I
10.1111/j.1600-065X.1998.tb01188.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-C(H)2-C(H)3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the C(H)2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the C(H)2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.
引用
收藏
页码:59 / 76
页数:18
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