Human IgG4: a structural perspective.

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Davies AM, Sutton BJ

Human IgG4: a structural perspective.

Immunol Rev. 2015 Nov;268(1):139-59. doi: 10.1111/imr.12349.

PubMed ID
26497518 [ View in PubMed
]
Abstract

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 Fcgamma receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcgamma 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 Cgamma2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcgammaRs.

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