In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 7, No. 73 ( 2022-07-08)
Abstract:
Monoclonal antibodies (mAbs) are powerful therapeutic agents. The agonistic activity of mAbs is dependent on the epitope recognized as well as the isotype. For human IgG2 mAbs, the structure of the hinge region is important for modulating agonistic activity, but the underlying mechanism is unclear. Orr et al. studied the structure and agonistic activity of a series of hIgG2 anti-CD40 cysteine to serine exchange variants. Agonistic activity varied depending on the pattern of disulfide bonds within the IgG2 hinge region, with more agonistic antibodies featuring a disulfide crossover, which directly affected the flexibility and the conformation of the antibody. mAbs with less flexible hinge regions had fewer conformations, which enabled increased receptor agonism. These findings highlight the importance of hinge variation in modulating antibody activity.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abm3723
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
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