2016
DOI: 10.1002/1873-3468.12284
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Self‐nonself discrimination by the complement system

Abstract: The alternative pathway (AP) of complement can recognize nonself structures by only two molecules, C3b and factor H. The AP deposits C3b covalently on nonself structures via an amplification system. The actual discrimination is performed by factor H, which has binding sites for polyanions (sialic acids, glycosaminoglycans, phospholipids). This robust recognition of ‘self’ protects our own intact viable cells and tissues, while activating structures are recognized by default. Foreign targets are opsonized for p… Show more

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Cited by 72 publications
(64 citation statements)
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References 136 publications
(160 reference statements)
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“…Furthermore, this study allowed the identification of key amino acid residues in FH CCP20 that bind the glycerol side chain and carboxyl group of Neu5Ac (i.e., the predominant form of sialic acid found in mammalian cells). Interestingly, CCP20 acts as a hot spot for HUS-associated mutations, which indeed modify the Neu5Ac-binding pocket and alter the overall affinity of FH for sialic acid [13], ultimately leading to the defective complement regulation observed in this pathology (see [25, 51]); see further details below.…”
Section: Interaction Of Factor H With Glycans—discriminating Self Fromentioning
confidence: 99%
See 1 more Smart Citation
“…Furthermore, this study allowed the identification of key amino acid residues in FH CCP20 that bind the glycerol side chain and carboxyl group of Neu5Ac (i.e., the predominant form of sialic acid found in mammalian cells). Interestingly, CCP20 acts as a hot spot for HUS-associated mutations, which indeed modify the Neu5Ac-binding pocket and alter the overall affinity of FH for sialic acid [13], ultimately leading to the defective complement regulation observed in this pathology (see [25, 51]); see further details below.…”
Section: Interaction Of Factor H With Glycans—discriminating Self Fromentioning
confidence: 99%
“…by RPE cells, as well as by the liver [21, 23]. Thus, systemic and locally secreted FH, most likely, both contribute to the regulation of complement activation in the context of immune surveillance [21, 24, 25]. …”
Section: Introductionmentioning
confidence: 99%
“…Specifically, the classical and the lectin pathways can recognize targets with specific pattern recognition molecules C1q, mannan-binding-lectin (MBL), and ficolins 1–3 (FCN1–3) (13). In contrast, the alternative pathway is continuously active and can amplify efficiently complement activation against non-self targets (24). All three pathways merge to activate the complement component C3, the most abundant complement factor in human blood plasma.…”
Section: Introductionmentioning
confidence: 99%
“…All these data point to a delicate balance of complement activation and inhibition necessary for homeostasis and prevention of harmful inflammation. The C-terminal domains of FH, especially the CCP20, are important for the interaction of the regulator with cell surface glycosaminoglycans and sialic acid as well as with C3b deposited during complement activation (30,(53)(54)(55)(56)(57)(58). These domains are conserved among FHR proteins, including FHR-B.…”
Section: Discussionmentioning
confidence: 99%