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Human IgG4: a structural perspective
Author(s) -
Davies Anna M.,
Sutton Brian J.
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12349
Subject(s) - antibody , subclass , degranulation , biology , fragment crystallizable region , effector , immunology , receptor , immunoglobulin fc fragments , cytotoxicity , fc receptor , immune system , immunoglobulin e , microbiology and biotechnology , immunoglobulin g , in vitro , biochemistry
Summary 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 Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ 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 Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs.