Human IgG subclasses (IgG1, IgG2, IgG3, IgG4) 

That discovery led to the IgG subclass system we rely on today: IgG1, IgG2, IgG3, and IgG4, named in order of decreasing serum abundance.

Although these subclasses share a common overall structure, they differ in the amino acid sequences of their heavy chains, resulting in distinct biological and effector functions.

Consequently, selecting the appropriate IgG subclass is a critical step in designing a therapeutic antibody, as it largely determines its mechanism of action.

IgG1: Strong Fcγ receptor (FcγR) and C1q binding → robust ADCC and CDC → the standard subclass for oncology therapeutics (e.g., trastuzumab, rituximab)

IgG2: Limited FcγR engagement → an emerging scaffold for co-stimulatory agonist antibodies (e.g., CD40, 4-1BB)

IgG3: The most potent effector subclass in vitro, but its short serum half-life (~7 days) has limited its therapeutic application.

IgG4: Minimal effector function → preferred for immune checkpoint inhibitors and allergy/immune-mediated diseases (e.g., pembrolizumab, dupilumab)

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