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J Biol Chem, Vol. 274, Issue 42, 29633-29640, October 15, 1999

Differential Binding of Histidine-rich Glycoprotein (HRG) to Human IgG Subclasses and IgG Molecules Containing  and  Light Chains

Nick N. Gorgani, Christopher R. Parish, and Joseph G. Altin^§

From the  Division of Immunology and Cell Biology, The John Curtin School of Medical Research and ^§ Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Science, The Australian National University, Canberra, Australian Capital Territory, 0200, Australia

In previous studies we showed that the plasma protein histidine-rich glycoprotein (HRG) binds strongly to pooled human IgG. In the present work myeloma proteins consisting of different human IgG subclasses were examined for their ability to interact with human HRG. Using an IAsys optical biosensor we found initially that IgG subclasses differ substantially in their affinity of interaction with HRG. However, the most striking finding was the observation that the kinetics of the HRG interaction was dramatically affected by whether the IgG subclasses contained the  or  light (L)-chains. Thus, the on-rate for the binding of HRG to the  L-chain containing IgG1 and IgG2 (IgG1 and IgG2) was ~4- and ~10-fold faster than that for the binding of HRG to  L-chain containing IgG1 and IgG2 (IgG1 and IgG2), respectively, with the dissociation constants (K_d) in the range 3-5 nM and 112-189 nM for the  and  isoforms, respectively. In contrast, the on-rate for the binding of HRG to IgG3 and IgG4 was found to be 9- and 20-fold slower than that for the binding of HRG to IgG3 and IgG4, respectively, with the K_d in the range 147-268 nM and 96-109 nM for the  and  isoforms, respectively. The binding of HRG to immunoglobulins containing the  L-chain (particularly IgG1) was generally potentiated in the presence of a physiological concentration (20 µM) of Zn²⁺ (K_d decreased to 0.60 ± 0.01 for IgG1), but Zn²⁺ had no effect or slightly inhibited the binding of HRG to immobilized IgG subclasses possessing the  L-chain. Interestingly, HRG also bound differentially to Bence Jones (BJ) proteins containing  and  L-chains, with HRG having a 14-fold lower K_d for BJ than for BJ when 20 µM Zn²⁺ was present. HRG also bound to IgM (IgM), but the affinity of this interaction (K_d ~1.99 ± 0.05 µM) was markedly lower than the interaction with IgG, and the affinity was actually decreased 4-fold in the presence of Zn²⁺. The results demonstrate that both the heavy (H)- and L-chain type have a profound effect on the binding of HRG to different IgG subclasses and provide the first evidence of a functional difference between the  and  L-chains of immunoglobulins.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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