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Intramolecular immunological signal hypothesis revived--structural background of signalling revealed by using Congo Red as a specific tool.

Jagusiak A, Konieczny L, Krol M, Marszalek P, Piekarska B, Piwowar P, Roterman I, Rybarska J, Stopa B, Zemanek G - Mini Rev Med Chem (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: .

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.

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Application of Congo red to reveal the signalling thresholdfor initiation of complement-driven hemolysis through enhancement ofimmune complexation and C1q binding. The effect is evidenced byusing combinations of the following components of the signallingsystem as independent reagents.
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Figure 6: Application of Congo red to reveal the signalling thresholdfor initiation of complement-driven hemolysis through enhancement ofimmune complexation and C1q binding. The effect is evidenced byusing combinations of the following components of the signallingsystem as independent reagents.

Mentions: In trying to confirm the presented hypothesis we focused on the effects of Congo red complexation on high-affinity antibodies, i.e. those which remain complexed when their low- affinity counterparts are washed out. Surprisingly, despite the lack of additional antibodies which might potentially form immune complexes (see Fig. 2), Congo red complexation was found to enhance hemolysis (Fig. 6).


Intramolecular immunological signal hypothesis revived--structural background of signalling revealed by using Congo Red as a specific tool.

Jagusiak A, Konieczny L, Krol M, Marszalek P, Piekarska B, Piwowar P, Roterman I, Rybarska J, Stopa B, Zemanek G - Mini Rev Med Chem (2015)

Application of Congo red to reveal the signalling thresholdfor initiation of complement-driven hemolysis through enhancement ofimmune complexation and C1q binding. The effect is evidenced byusing combinations of the following components of the signallingsystem as independent reagents.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440395&req=5

Figure 6: Application of Congo red to reveal the signalling thresholdfor initiation of complement-driven hemolysis through enhancement ofimmune complexation and C1q binding. The effect is evidenced byusing combinations of the following components of the signallingsystem as independent reagents.
Mentions: In trying to confirm the presented hypothesis we focused on the effects of Congo red complexation on high-affinity antibodies, i.e. those which remain complexed when their low- affinity counterparts are washed out. Surprisingly, despite the lack of additional antibodies which might potentially form immune complexes (see Fig. 2), Congo red complexation was found to enhance hemolysis (Fig. 6).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: .

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.

Show MeSH