The dynamic assembly of antibodies for recruiting complements on an antigenic membrane.
Antibodies are key players in our immune system. These antibodies recognize antigens displayed on foreign cell membranes and thereby recruit attacking forces, called complements. This mechanism is detrimental to our own immune system at times when our own cells exhibit some molecules that resemble infectious bacterial ones. Guillain–Barré syndrome is a postinfectious autoimmune disorder which is characterized by antibodies misdirected against GM1, self-molecule found in our neuronal cells. Although molecular mimicry between GM1 and the infectious bacterial lipo-oligosaccharide has been proven, the detailed mechanisms linking autoantigen recognition and complement activation remain unexplored.
The collaborative groups, including researchers at Exploratory Research Center on Life and Living Systems (ExCELLS) and Institute for Molecular Science (IMS) of National Institutes of Natural Sciences and Graduate School of Pharmaceutical Sciences of Nagoya City University investigated this mechanism utilizing high-speed atomic force microscopy. They successfully visualized the dynamic process by which the autoantibodies that are bound to GM1 contained in membranes spontaneously assemble to form a hexameric ring structure on the membrane. They also revealed that the assembled antibodies serve as a landing place for the first charge commander C1q on the membrane, which is the initial step of complement-mediated cell lysis. The groups’ findings will provide deep insights into the molecular mechanisms behind Guillain–Barré syndrome and offer clues for controlling antibody assembly and consequent complement activation.
The antibodies assembled into a hexameric ring (white circle) transiently interact with the complement component C1q (white arrow) on the membrane containing GM1 as antigen.
Journal
Journal: International Journal of Molecular Sciences
Title: On-Membrane Dynamic Interplay between Anti-GM1 IgG Antibodies and Complement Component C1q
Author: Saeko Yanaka,Rina Yogo,Hiroki Watanabe,Yuki Taniguchi,Tadashi Satoh,Naoko Komura,Hiromune Ando,Hirokazu Yagi,Nobuhiro Yuki,Takayuki Uchihashi,and Koichi Kato
DOI: 10.3390/ijms21010147
Eurekalert! URL:https://www.eurekalert.org/pub_releases/2020-01/nion-aga010620.php
Article URL: https://www.mdpi.com/1422-0067/21/1/147
Contact
Koichi Kato
Exploratory Research Center on Life and Living Systems (ExCELLS)/
Institute for Molecular Science, Natural Institutes of Natural Sciences
TEL: +81-564-59-5225
E-mail: kkato_at_excells.orion.ac.jp (Please replace the “_at_” with @)