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Human IgG2 Antibodies Display Disulfide-Mediated Structural Isoforms

Human IgG2 Antibodies Display Disulfide-Mediated Structural Isoforms

Jette Wypych, Ming Li, Amy Guo, Zhongqi Zhang, Theresa Martinez, Martin J Allen, Szilan Fodor, Drew N Kelner, Gregory C Flynn, Yaoqing Diana Liu, Pavel V Bondarenko, Margaret Speed Ricci, Thomas M Dillon, etc.

J Biol Chem. 2008 Jun 6;283(23):16194-205.

PMID: 18339624

Abstract:

In this work, we present studies of the covalent structure of human IgG2 molecules. Detailed analysis showed that recombinant human IgG2 monoclonal antibody could be partially resolved into structurally distinct forms caused by multiple disulfide bond structures. In addition to the presently accepted structure for the human IgG2 subclass, we also found major structures that differ from those documented in the current literature. These novel structural isoforms are defined by the light chain constant domain (C(L)) and the heavy chain C(H)1 domain covalently linked via disulfide bonds to the hinge region of the molecule. Our results demonstrate the presence of three main types of structures within the human IgG2 subclass, and we have named these structures IgG2-A, -B, and -A/B. IgG2-A is the known classic structure for the IgG2 subclass defined by structurally independent Fab domains and hinge region. IgG2-B is a structure defined by a symmetrical arrangement of a (C(H)1-C(L)-hinge)(2) complex with both Fab regions covalently linked to the hinge. IgG2-A/B represents an intermediate form, defined by an asymmetrical arrangement involving one Fab arm covalently linked to the hinge through disulfide bonds. The newly discovered structural isoforms are present in native human IgG2 antibodies isolated from myeloma plasma and from normal serum. Furthermore, the isoforms are present in native human IgG2 with either kappa or lambda light chains, although the ratios differ between the light chain classes. These findings indicate that disulfide structural heterogeneity is a naturally occurring feature of antibodies belonging to the human IgG2 subclass.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411680	IgG2, Kappa from human myeloma plasma			Price

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