title: Intramolecular immunological signal hypothesis revived--structural background of signalling revealed by using Congo Red as a specific tool.
abstract: Micellar structures formed by self-assembling Congo red molecules bind to proteins penetrating into function-related unstable packing areas. Here, we have used Congo red--a supramolecular protein ligand--to investigate how the intramolecular structural changes that take place in antibodies following antigen binding lead to complement activation. According to our findings, Congo red binding significantly enhances the formation of antigen-antibody complexes. As a result, even low-affinity transiently binding antibodies can participate in immune complexes in the presence of Congo red, although immune complexes formed by these antibodies fail to trigger the complement cascade. This indicates that binding of antibodies to the antigen may not, by itself, fulfill the necessary conditions to generate the signal which triggers effector activity. These findings, together with the results of molecular dynamics simulation studies, enable us to conclude that, apart from the necessary assembling of antibodies, intramolecular structural changes generated by strains which associate high- affinity bivalent antibody fitting to antigen determinants are also required to cross the complement activation threshold.
authors.affiliation: .
authors.forename: A
authors.initials: A
authors.lastname: Jagusiak
authors.affiliation: .
authors.forename: L
authors.initials: L
authors.lastname: Konieczny
authors.affiliation: .
authors.forename: M
authors.initials: M
authors.lastname: Krol
authors.affiliation: .
authors.forename: P
authors.initials: P
authors.lastname: Marszalek
authors.affiliation: .
authors.forename: B
authors.initials: B
authors.lastname: Piekarska
authors.affiliation: .
authors.forename: P
authors.initials: P
authors.lastname: Piwowar
authors.affiliation: .
authors.forename: I
authors.initials: I
authors.lastname: Roterman
authors.affiliation: .
authors.forename: J
authors.initials: J
authors.lastname: Rybarska
authors.affiliation: .
authors.forename: B
authors.initials: B
authors.lastname: Stopa
authors.affiliation: Department of Bioinformatics and Telemedicine, Jagiellonian University, Medical College, Lazarza 16, 31- 530 Krakow, Poland.. myroterm@cyf-kr.edu.pl.
authors.forename: G
authors.initials: G
authors.lastname: Zemanek
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D003224:Congo Red / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D003224:Congo Red