Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H.

Two mouse monoclonal antibodies against the human complement control protein, Factor H (β1H), are described. The antibodies are both IgG − γ1 - subclasses and are directed against different epitopes on the human Factor H molecule. One of the antibodies, MRC OX 24, increases the cofactor activity of Factor H in Factor I-mediated cleavage of soluble C3b. The second antibody, MRC OX 23, which has no effect alone, reduces the increase in cofactor activity observed in the presence of the first antibody. However, MRC OX 24 inhibits the binding of 125I-labelled Factor H to surface-bound C3b (EAC3b). Again MRC OX 23 alone does not have any effect but decreases the inhibition in 125I-Labelled Factor H binding to EAC3b observed with MRC OX 24. These studies show clearly that the interaction of Factor H with soluble C3b is different to its interaction with surface-bound C3b. In an indirect immunoprecipitation system using these monoclonal antibodies, single-chain molecules of 150 000 mol. wt. are specifically precipitated from human serum and also from the sera of other primates - rhesus monkey, cynomolgus monkey, and African green monkey. There was no precipitation from sera of cow, pig, sheep, chick, or rabbit. Using a radioimmunoassay with radiolabelled monoclonal MRC OX 23, the concentration of Factor H in human plasma was determined.

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SP105ATYPICAL HEMOLYTIC UREMIC SYNDROME AND C3 GLOMERULOPATHY DUE TO MONOCLONAL ANTIBODY AGAINST COMPLEMENT CONTROL PROTEIN FACTOR H

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz103.sp105 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Paraskevi Eva Andronikidis ◽

Papanikolaou Vasiliki ◽

Plavoukou Styliani ◽

Tsouka Glykeria ◽

Delibasi Sosanna ◽

...

Keyword(s):

Monoclonal Antibody ◽

Hemolytic Uremic Syndrome ◽

Factor H ◽

C3 Glomerulopathy ◽

Complement Control Protein ◽

Protein Factor ◽

Uremic Syndrome ◽

Control Protein

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Complement control protein factor H: The good, the bad, and the inadequate

Molecular Immunology ◽

10.1016/j.molimm.2010.05.007 ◽

2010 ◽

Vol 47 (13) ◽

pp. 2187-2197 ◽

Cited By ~ 204

Author(s):

Viviana P. Ferreira ◽

Michael K. Pangburn ◽

Claudio Cortés

Keyword(s):

Factor H ◽

Complement Control Protein ◽

Protein Factor ◽

Control Protein

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Utilising ion mobility-mass spectrometry to interrogate macromolecules: Factor H complement control protein modules 10–15 and 19–20 and the DNA-binding core domain of tumour suppressor p53

International Journal of Mass Spectrometry ◽

10.1016/j.ijms.2010.01.007 ◽

2010 ◽

Vol 298 (1-3) ◽

pp. 99-110 ◽

Cited By ~ 14

Author(s):

Peter A. Faull ◽

Hannah V. Florance ◽

Christoph Q. Schmidt ◽

Nick Tomczyk ◽

Paul N. Barlow ◽

...

Keyword(s):

Mass Spectrometry ◽

Ion Mobility ◽

Factor H ◽

Ion Mobility Mass Spectrometry ◽

Core Domain ◽

Complement Control Protein ◽

Binding Core ◽

Tumour Suppressor P53 ◽

Protein Modules ◽

Control Protein

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A common site within factor H SCR 7 responsible for binding heparin, C-reactive protein and streptococcal M protein

Immunopharmacology ◽

10.1016/s0162-3109(00)80162-9 ◽

2000 ◽

Vol 49 (1-2) ◽

pp. 57 ◽

Cited By ~ 2

Author(s):

E. Giannakis ◽

D.A. Male ◽

R.J. Ormsby ◽

C. Mold ◽

S. Ranganathan ◽

...

Keyword(s):

Factor H ◽

M Protein ◽

C Reactive Protein ◽

Common Site ◽

Reactive Protein ◽

Streptococcal M Protein

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Affinity Purification of Human Factor H on Polypeptides Derived from Streptococcal M Protein: Enrichment of the Y402 Variant

PLoS ONE ◽

10.1371/journal.pone.0081303 ◽

2013 ◽

Vol 8 (11) ◽

pp. e81303 ◽

Cited By ~ 1

Author(s):

O. Rickard Nilsson ◽

Jonas Lannergård ◽

B. Paul Morgan ◽

Gunnar Lindahl ◽

Mattias C. U. Gustafsson

Keyword(s):

Human Factor ◽

Affinity Purification ◽

Factor H ◽

M Protein ◽

Protein Enrichment ◽

Streptococcal M Protein

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M Protein of the Group A StreptococcusBinds to the Seventh Short Consensus Repeat of Human Complement Factor H

Infection and Immunity ◽

10.1128/iai.66.4.1427-1431.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1427-1431 ◽

Cited By ~ 69

Author(s):

Timothy K. Blackmore ◽

Vincent A. Fischetti ◽

Tania A. Sadlon ◽

Helena M. Ward ◽

David L. Gordon

Keyword(s):

Protein Binding ◽

Binding Site ◽

Regulatory Protein ◽

Factor H ◽

M Protein ◽

Protein Binding Site ◽

Enzyme Linked Immunosorbent Assay ◽

Complement Factor ◽

Heparin Binding ◽

Protein Factor

ABSTRACT Streptococcus pyogenes evades complement by binding the complement-regulatory protein factor H (fH) via the central conserved C-repeat region of M protein. However, the corresponding binding region within fH has not previously been precisely localized. fH is composed of 20 conserved modules called short consensus repeats (SCRs), each of which contains approximately 60 amino acids. A series of fH truncated and deletion mutants were prepared, and their interaction with M6 protein was examined. The M protein binding site was initially localized to SCRs 6 to 15 as demonstrated by ligand dot blotting, chemical cross-linking, and enzyme-linked immunosorbent assay. SCR 7 was then shown to contain the M protein binding site, as a construct consisting of the first seven SCRs bound M protein but a construct containing the first six SCRs did not bind. In addition, deletion of SCR 7 from full-length fH abolished binding to M protein. SCR 7 is known to contain a heparin binding domain, and binding of fH to M6 protein was almost totally inhibited in the presence of 400 U of heparin per ml. These results localize the M6 protein binding site of fH to SCR 7 and indicate that it is in close proximity to the heparin binding site.

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Solution structure of the fifth repeat of factor H: a second example of the complement control protein module

Biochemistry ◽

10.1021/bi00129a011 ◽

1992 ◽

Vol 31 (14) ◽

pp. 3626-3634 ◽

Cited By ~ 80

Author(s):

P. N. Barlow ◽

D. G. Norman ◽

A. Steinkasserer ◽

T. J. Horne ◽

J. Pearce ◽

...

Keyword(s):

Solution Structure ◽

Factor H ◽

Complement Control Protein ◽

Control Protein

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Clumping Factor A Interaction with Complement Factor I Increases C3b Cleavage on the Bacterial Surface of Staphylococcus aureus and Decreases Complement-Mediated Phagocytosis

Infection and Immunity ◽

10.1128/iai.01065-09 ◽

2010 ◽

Vol 78 (4) ◽

pp. 1717-1727 ◽

Cited By ~ 65

Author(s):

Pamela S. Hair ◽

Charlene G. Echague ◽

Amber M. Sholl ◽

Justin A. Watkins ◽

Joan A. Geoghegan ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Surface Protein ◽

Factor H ◽

Complement Factor ◽

Wild Type ◽

Bacterial Surface ◽

Complement Control Protein ◽

Factor I ◽

Protein Factor ◽

Fibrinogen Binding

ABSTRACT The human complement system is important in the immunological control of Staphylococcus aureus infection. We showed previously that S. aureus surface protein clumping factor A (ClfA), when expressed in recombinant form, bound complement control protein factor I and increased factor I cleavage of C3b to iC3b. In the present study, we show that, compared to the results for the wild type, when isogenic ClfA-deficient S. aureus mutants were incubated in serum, they bound less factor I, generated less iC3b on the bacterial surface, and bound fewer C3 fragments. It has been shown previously that two amino acids in ClfA (P336 and Y338) are essential for fibrinogen binding. However, S. aureus expressing ClfA(P336A Y338S) was less virulent than ClfA-deficient strains in animal models. This suggested that ClfA contributed to S. aureus virulence by a mechanism different than fibrinogen binding. In the present study, we showed that S. aureus expressing ClfA(P336A Y338S) was more susceptible to complement-mediated phagocytosis than a ClfA-null mutant or the wild type. Unlike ClfA, ClfA(P336A Y338S) did not enhance factor I cleavage of C3b to iC3b and inhibited the cofactor function of factor H. Fibrinogen enhanced factor I binding to ClfA and the S. aureus surface. Twenty clinical S. aureus strains all expressed ClfA and bound factor I. High levels of factor I binding by clinical strains correlated with poor phagocytosis. In summary, our results suggest that the interaction of ClfA with factor I contributes to S. aureus virulence by a complement-mediated mechanism.

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