Human IgG4: a structural perspective #MMPMID26497518
Davies AM; Sutton BJ
Immunol Rev 2015[Nov]; 268 (1): 139-59 PMID26497518show ga
IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1-mediated anti-tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fc? receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fc? receptors, and structures for intact antibodies, high-resolution crystal structures were not reported for IgG4-Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4-Fc. We discuss the unexpected conformations adopted by functionally important C?2 domain loops, and speculate about potential implications for the interaction between IgG4 and Fc?Rs.
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Immunol+Rev 2015 ; 268 (1): 139-59
