The interaction of soluble human complement receptor type 1 (sCR1, BRL55730) with human complement component C4

Gibb, A; Freeman, Anne; Smith, Richard A.; Edmonds, S. J.; Sim, Edith

doi:10.1016/0925-4439(93)90056-7

Cited by 18 publications

(11 citation statements)

References 36 publications

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“…In this way, it was possible to achieve a meaningful degree of binding site saturation for what is well established to be a highly salt-sensitive interaction (10,24). Although it is reasonable to have some concern about extrapolating our results to physiologic ionic strength, we note that in one of the earlier studies that reported higher sCR1 binding of a thioester-cleaved form of C4A relative to C4B, the authors stated that the binding difference was actually accentuated at low ionic strength (24).…”

Section: Discussionmentioning

confidence: 99%

“…The study of Gibb et al (24) used ammonia treatment of C4A and C4B to cleave the thioester bond and induce a C4b-like conformation. When equal amounts of ammonia-treated C4A and C4B were coated onto ELISA wells, it was found that the binding of 125 I-labeled sCR1 was ϳ2-fold greater to the C4A material than to C4B.…”

Section: Discussionmentioning

confidence: 99%

“…Other functional properties, including cleavage rate by C1 s, classical pathway C3 convertase subunit activity, regulation by complement factor I (fI) in the presence of C4b-binding protein (C4BP), and ability to act as a transacylation acceptor for C3b in the formation of the classical pathway C5 convertase, were found not to differ substantially between C4A and C4B (13,14,22). However, there have been three reports concluding that C4Ab (or, in one case, ammonia-treated C4A, a thioester-cleaved C4b-like species) displayed higher binding to CR1 than did C4Bb, or ammonia-treated C4B (23)(24)(25). The study by Reilly and Mold (25) used isotypic forms of covalent dimers of human C4b fragment, in which the cross-link was via the liberated thioester cysteine, to actually measure equilibrium-binding constants.…”

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confidence: 99%

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The C4A and C4B Isotypic Forms of Human Complement Fragment C4b Have the Same Intrinsic Affinity for Complement Receptor 1 (CR1/CD35)

Clemenza

Isenman

2004

The Journal of Immunology

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Several previous reports concluded that the C4b fragment of human C4A (C4Ab) binds with higher affinity to CR1 than does C4Bb. Because the isotypic residues, 1101PCPVLD and 1101LSPVIH in C4A and C4B, respectively, are located within the C4d region, one may have expected a direct binding contribution of C4d to the interaction with CR1. However, using surface plasmon resonance as our analytical tool, with soluble rCR1 immobilized on the biosensor chip, we failed to detect significant binding of C4d of either isotype. By contrast, binding of C4c was readily detectable. C4A and C4B, purified from plasma lacking one of the isotypes, were C1̄s converted to C4Ab and C4Bb. Spontaneously formed disulfide-linked dimers were separated from monomers and higher oligomers by sequential chromatographic steps. The binding sensorgrams of C4Ab and C4Bb monomers as analytes reached steady state plateaus, and these equilibrium data yielded essentially superimposable saturation curves that were well fit by a one-site binding model. Although a two-site model was required to fit the equilibrium-binding data for the dimeric forms of C4b, once again there was little difference in the KD values obtained for each isotype. Independent verification of our surface plasmon resonance studies came from ELISA-based inhibition experiments in which monomers of C4Ab and C4Bb were equipotent in inhibiting the binding of soluble CR1 to plate-bound C4b. Although divergent from previous reports, our results are consistent with recent C4Ad structural data that raised serious doubts about there being a conformational basis for the previously reported isotypic differences in the C4b-CR1 interaction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The C4A and C4B Isotypic Forms of Human Complement Fragment C4b Have the Same Intrinsic Affinity for Complement Receptor 1 (CR1/CD35)

Clemenza

Isenman

2004

The Journal of Immunology

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“…While C3b is considered the major binding ligand of CR1, the importance of C4b in generating C3b is underscored by the fact that congenital deficiency of C4 is linked to immune complex diseases, such as SLE [7,8]. Furthermore, C4A, but not C4B, null alleles are strongly associated with SLE, suggesting that they may function differently in either the binding to immune complexes [18-221 and/or interaction with CRl [23,24,26].…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

Reilly

Mold

1997

Clinical and Experimental Immunology

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SUMMARYComplement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4bK3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CRI binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab-and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CRI showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd = 1 . 4~ low7 M) than C4Bb2 (Kd = 4.8 x M), indicating a preferential binding of CR 1 for C4A.

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“…While the reaction rate of activated C4A toward its targets is about four times slower than that of activated C4B, the isotypic residues also confer on C4Ab a relatively longer half-life against hydrolysis (~10 s) (Sepp et al, 1993) and a higher affinity for complement receptor CR1 (Gatenby et al, 1990;Gibb et al, 1993;Reilly and Mold, 1997). Therefore, it is thought that C4A is important in the solubilization of immune aggregates, immunoclearance, and opsonization.…”

Section: Diversity Of Human C4a and C4b Proteinsmentioning

confidence: 99%

Molecular Autoimmunity

2005

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The interaction of soluble human complement receptor type 1 (sCR1, BRL55730) with human complement component C4

Cited by 18 publications

References 36 publications

The C4A and C4B Isotypic Forms of Human Complement Fragment C4b Have the Same Intrinsic Affinity for Complement Receptor 1 (CR1/CD35)

The C4A and C4B Isotypic Forms of Human Complement Fragment C4b Have the Same Intrinsic Affinity for Complement Receptor 1 (CR1/CD35)

Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

Molecular Autoimmunity

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