Journal article

Publication year: 2018

Journal: Infection and Immunity

Volume number: 86

Issue number: 8

ISSN: 0019-9567

eISSN: 1098-5522

DOI Link: https://doi.org/10.1128/IAI.00924-18

Publisher: American Society for Microbiology

Abstract: 
The Fc gamma receptor IIIb (Fc gamma RIIIb) is a low-affinity receptor of IgG and is essential in neutrophil-mediated effector functions. Different allelic forms of Fc gamma RIIIb carrying human neutrophil antigen (HNA-1a, -1b, -1c, and -1d) have been identified. Here, we have generated stable transfected HEK293 cell lines expressing HNA-1aa, -1bb, and -1bc. Of these, cells expressing HNA-1bc interacted significantly stronger (binding affinities, 2.277 versus 0.743) with human IgG than cells expressing the HNA-1aa or -1bb alloforms. The higher affinity of IgG toward the HNA-1c alloform was confirmed using neutrophils derived from German blood donors. Neutrophils from HNA-1abc-phenotyped individuals bound IgG significantly stronger (1.825 versus 0.903) than did neutrophils from HNA-1ab-typed individuals. These findings were confirmed by surface plasmon resonance (SPR) analysis demonstrating that recombinant HNA-1bc had a higher affinity (dissociation constant [K-d], 7.24 x 10(-6) M) than recombinant HNA-1bb (K-d, 1.15 x 10(-5) M) against normal IgG. Finally, we demonstrated that Plasmodium falciparum merozoites opsonized with human IgG affinity purified against P. falciparum glutamate-rich protein (GLURP) enhanced stronger reactive oxygen species (ROS) emission in neutrophils obtained from HNA-1abc donors than in neutrophils from HNA-1ab donors. Collectively, these results indicate that the amino acid substitution Ala(78)Asp resulting in the HNA-1c allotype leads to higher affinity toward human IgG, enhancement of neutrophil activation, and possibly effective clearance of malaria by intracellular ROS.

Harvard Citation style: Simtong, P., Romphruk, A., Traum, A., Burg-Roderfeld, M., Bein, G., Jakubowski, K., et al. (2018) Molecular and Functional Characterization of Fcγ Receptor IIIb-Ligand Interaction: Implications for Neutrophil-Mediated Immune Mechanisms in Malaria, Infection and Immunity, 86(8), Article e00924-18. https://doi.org/10.1128/IAI.00924-18

APA Citation style: Simtong, P., Romphruk, A., Traum, A., Burg-Roderfeld, M., Bein, G., Jakubowski, K., Dominik, A., Theisen, M., Kana, I., Sachs, U., & Santoso, S. (2018). Molecular and Functional Characterization of Fcγ Receptor IIIb-Ligand Interaction: Implications for Neutrophil-Mediated Immune Mechanisms in Malaria. Infection and Immunity. 86(8), Article e00924-18. https://doi.org/10.1128/IAI.00924-18