Reaction between the isolated globular sub-units of the complement component Clq and IgG-complexes

Hughes‐Jones, N. C.; Gardner, Brigitte

doi:10.1016/0161-5890(79)90010-5

Cited by 127 publications

(64 citation statements)

References 13 publications

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“…Five mAbs turned out to be directed to the C1qGR, and these mAbs inhibited the binding of C1q to solid-phase IgG, in agreement with the notion that the binding sites on C1q for IgG are located in the GR (16,17). Moreover, competition experiments not shown here revealed that these five mAbs were directed against at least two different epitopes on the globular region of C1q.…”

Section: Discussionmentioning

confidence: 63%

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Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

McGrath

Brouwer

Arlaud

et al. 2006

The Journal of Immunology

118

101

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C1q acts as the recognition unit of the first complement component, C1, and binds to immunoglobulins IgG and IgM, as well as to non-Ig ligands, such as C-reactive protein (CRP). IgG and IgM are recognized via the globular head regions of C1q (C1qGR), whereas CRP has been postulated to interact with the collagen-like region (C1qCLR). In the present study, we used a series of nine mAbs to C1q, five directed against C1qGR and four against C1qCLR, to inhibit the interaction of C1q with CRP. The F(ab′)2 of each of the five mAbs directed against C1qGR inhibited binding of C1q to polymerized IgG. These five mAbs also successfully inhibited the interaction of C1q with CRP. Moreover, these five mAbs inhibited C1 activation by CRP as well as by polymerized IgG in vitro. In contrast, none of the four mAbs against C1qCLR inhibited C1q interaction with CRP or IgG, or could reduce activation of complement by CRP or polymerized IgG. These results provide the first evidence that the interaction of C1q with CRP or IgG involves sites located in the C1qGR, whereas sites in the CLR do not seem to be involved in the physiological interaction of C1q with CRP.

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Section: Discussionmentioning

confidence: 63%

“…C1q can bind various activators such as immunoglobulins IgG (16) and IgM (17), as well as non-Ig proteins like CRP (7), SAP (18), PTX3 (19), and ␤-amyloid fibrils (A␤) (20). A common binding site on C1q for all these activators may serve as target for potential inhibitors.…”

mentioning

confidence: 99%

Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

McGrath

Brouwer

Arlaud

et al. 2006

The Journal of Immunology

118

101

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“…Based on all of the best fit structures, the mean obstructed volume for IgG1 6a-C1q was 6.9 nm 3 , that for IgG1 19a-C1q was 2. (63,64). Localized IgG clusters may bind a C1q hexamer through multivalent contacts to increase the strength of the C1q-Fc interaction, as exemplified by a hexamer configuration of an IgG1 mutant (65).…”

Section: Discussionmentioning

confidence: 99%

The Solution Structures of Two Human IgG1 Antibodies Show Conformational Stability and Accommodate Their C1q and FcγR Ligands

Rayner

Hui

Gor

et al. 2015

Journal of Biological Chemistry

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Background:The human IgG1 antibody subclass is the most abundant one and is widely used in therapeutic applications. Results: Ultracentrifugation and x-ray/neutron scattering, together with atomistic modeling, revealed asymmetric concentration-independent IgG1 solution structures. Conclusion:The complement and receptor Fc binding sites are not hindered by the Fab regions, explaining its full activity. Significance: These solution structures clarify IgG1 activity and its therapeutic applications.

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“…It is initiated by the binding of C1q, a constituent of the first component of complement, to the C H 2 domain of Igs, IgG and IgM, which are in complex with Ag (1,2). The C1q binding epicenter in the C H 2 domain of human IgG1 has recently been mapped by site-directed mutagenesis (3).…”

mentioning

confidence: 99%

Engineered Antibodies with Increased Activity to Recruit Complement

Idusogie¹,

Wong²,

Presta³

et al. 2001

The Journal of Immunology

266

168

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This manuscript describes two sites in a human IgG1 that, when mutated individually or in combination, result in a dramatic increase in C1q binding and complement-dependent cytotoxicity activity. These two residues, K326 and E333, are located at the extreme ends of the C1q binding epicenter in the CH2 domain of a human IgG. A mutation to tryptophan at K326 debilitates Ab-dependent cell-mediated cytotoxicity activity. In addition, substitutions of the residues E333 with serine and of K326 with tryptophan in a human IgG2 confer biological activity in the complement-dependent cytotoxicity assay in which the wild-type IgG2 is inactive. This study reveals that the residues K326 and E333 play a significant role in the control of the biological activity of an IgG molecule and can rescue the activity of an inactive IgG isotype.

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Reaction between the isolated globular sub-units of the complement component Clq and IgG-complexes

Cited by 127 publications

References 13 publications

Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

The Solution Structures of Two Human IgG1 Antibodies Show Conformational Stability and Accommodate Their C1q and FcγR Ligands

Engineered Antibodies with Increased Activity to Recruit Complement

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