2020
DOI: 10.4049/jimmunol.2000752
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A Complement C3–Specific Nanobody for Modulation of the Alternative Cascade Identifies the C-Terminal Domain of C3b as Functional in C5 Convertase Activity

Abstract: The complement system is an intricate cascade of the innate immune system and plays a key role in microbial defense, inflammation, organ development, and tissue regeneration. There is increasing interest in developing complement regulatory and inhibitory agents to treat complement dysfunction. In this study, we describe the nanobody hC3Nb3, which is specific for the C-terminal C345c domain of human and mouse complement component C3/C3b/C3c and potently inhibits C3 cleavage by the alternative pathway. A high-re… Show more

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Cited by 13 publications
(19 citation statements)
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“…To gain further insight into the apparent inhibition of the CP/LP C5 convertase, the effect of the nanobody on CP mediated lysis of sheep erythrocytes was tested. Similar to the C5b-9 deposition assays, hC3Nb3 efficiently reduced CP driven hemolysis [101] ( Figure 5C). To exclude that this effect was due to residual AP activity, we also performed experiments in FB depleted serum that does not allow the assembly of the AP C3 convertase.…”
Section: Hc3nb3 Provides Insight Into the Role Of C3b In C5 Convertasessupporting
confidence: 64%
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“…To gain further insight into the apparent inhibition of the CP/LP C5 convertase, the effect of the nanobody on CP mediated lysis of sheep erythrocytes was tested. Similar to the C5b-9 deposition assays, hC3Nb3 efficiently reduced CP driven hemolysis [101] ( Figure 5C). To exclude that this effect was due to residual AP activity, we also performed experiments in FB depleted serum that does not allow the assembly of the AP C3 convertase.…”
Section: Hc3nb3 Provides Insight Into the Role Of C3b In C5 Convertasessupporting
confidence: 64%
“…Complement component C3 constitutes the point of convergence between the three pathways of the complement system, and C3 is a common target for complete inhibition of the complement cascade [89,90]. To date, we have described the three C3 specific nanobodies hC3Nb1 [99], hC3Nb2 [100] and hC3Nb3 [101]. Both hC3Nb1 and hC3Nb3 prevent the zymogen FB from binding to C3b by direct competition and inhibit C3 degradation through the alternative pathway.…”
Section: The Hc3nb1 Is An Inhibitor Of Ap Proconvertase Assemblymentioning
confidence: 99%
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“…Complement component C3 constitutes the point of convergence between the three pathways of the complement system, and C3 is a common target for complete inhibition of the complement cascade [ 88 , 89 ]. To date, we have described the three C3 specific nanobodies hC3Nb1 [ 99 ], hC3Nb2 [ 100 ] and hC3Nb3 [ 101 ]. Both hC3Nb1 and hC3Nb3 prevent the zymogen FB from binding to C3b by direct competition and inhibit C3 degradation through the alternative pathway.…”
Section: The Complement-targeting Nanobodiesmentioning
confidence: 99%