scholarly journals The importance of the location of antibody binding on the M6 protein for opsonization and phagocytosis of group A M6 streptococci.

1988 ◽  
Vol 167 (3) ◽  
pp. 1114-1123 ◽  
Author(s):  
K F Jones ◽  
V A Fischetti
Keyword(s):  
Complement Fixation ◽  
Hypervariable Region ◽  
Antibody Binding ◽  
Factor H ◽  
Complement Factor ◽  
Amino Terminal ◽  
Group A ◽  
Native Group ◽  
Binding Titer

One of 19 mAbs against the native group A streptococcal M6 protein proved opsonic for type 6 organisms in a bactericidal assay. The opsonic and three nonopsonic antibodies were selected for isotype and complement fixation studies based on previous knowledge of their epitope site on the M6 molecule. While mAb 3B8 (IgG3), whose epitope is in the NH2-terminal hypervariable region of the molecule (distal from the cell), and mAbs 10B6 (IgG2a) and 10F5 (IgG2b), both located in the conserved central region of the molecule, all fix complement, 10A11 (IgG1) did not. Only mAb 3B8 was opsonic despite the fact that mAbs 10B6 and 10F5 both exhibited similar complement-fixing capacity, binding titer, and surface exposure of epitopes. Analysis of antibodies raised against synthetic peptides representing various regions of the M6 protein showed that only the amino-terminal peptide (residues 1-21) was capable of eliciting opsonic antibodies, despite the fact that peptides from other areas produced antibodies with high-binding titers to the native M6 protein and also with the ability to bind to intact streptococcal cells. These results not only support the observed type specificity of opsonic antibodies, but also clearly point to the importance of the location of antibody binding on the M molecule relative to the actual functional capacity of the antibody with respect to the opsonization and phagocytosis of M6 streptococci. These results may underscore the recently observed role of complement Factor H in the antiphagocytic activity of the M protein.

Identification and characterization of a new cell surface protein possessing factor H-binding activity in the swine pathogen and zoonotic agent Streptococcus suis

2013 ◽  
Vol 62 (7) ◽  
pp. 1073-1080 ◽  
Author(s):  
Katy Vaillancourt ◽  
Laetitia Bonifait ◽  
Louis Grignon ◽  
Michel Frenette ◽  
Marcelo Gottschalk ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Protein ◽  
Streptococcus Suis ◽  
Binding Activity ◽  
Factor H ◽  
Complement Factor ◽  
Cell Surface Protein ◽  
Amino Terminal ◽  
Swine Pathogen ◽  
Complement Regulator

Streptococcus suis is a major swine pathogen and an emerging zoonotic agent. The ability of pathogenic bacteria to bind the complement regulator factor H on their cell surface may allow them to avoid complement attack and phagocytosis. The aim of this study was to characterize a new cell surface protein possessing factor H-binding activity in S. suis serotype 2. The capacity of S. suis to bind the complement regulator factor H on its surface was demonstrated by ELISA. Using a factor I–cofactor assay, it was found that the functional activity of factor H bound to S. suis was kept. Since the product of gene SSU0186 in S. suis P1/7 shared similarity with a Streptococcus pneumoniae protein (named PspC) possessing factor H-binding activity, it was proposed as a putative factor H receptor in S. suis. SSU0186 has a 1686 bp open reading frame encoding a 561 amino acid protein containing the Gram-positive cell wall anchoring motif (LPXTG) at the carboxy-terminal, an amino-terminal signal sequence, an α-helix domain, a proline-rich region and a G5 domain. The SSU0186 gene was cloned in Escherichia coli and the purified recombinant factor H-binding protein showed a molecular mass of 95 kDa, as determined by SDS-PAGE. The protein possessed the functional property of binding factor H. Sera from S. suis-infected pigs reacted with the recombinant factor H receptor, suggesting that it is produced during the course of infections. In conclusion, we identified a novel S. suis cell surface protein that binds the complement factor H. This cell surface protein may help S. suis to resist complement attack and phagocytosis and contribute to pathogenesis.

The role of complement factor H and clusterin in obstructive sleep apnoea

2020 ◽  
Author(s):  
Andras Bikov ◽  
Martina Meszaros ◽  
Peter Horvath ◽  
Zsofia Lazar ◽  
David Tarnoki ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Sleep Apnoea ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Obstructive Sleep

scholarly journals A potential anti-coagulant role of complement factor H

2014 ◽  
Vol 59 (2) ◽  
pp. 188-193 ◽  
Author(s):  
Janez Ferluga ◽  
Uday Kishore ◽  
Robert. B. Sim
Keyword(s):  
Factor H ◽  
Complement Factor H ◽  
Complement Factor

scholarly journals The Role of Complement in Age-Related Macular Degeneration: Heparan Sulphate, a ZIP Code for Complement Factor H?

2013 ◽  
Vol 6 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Alex Langford-Smith ◽  
Tiarnan D.L. Keenan ◽  
Simon J. Clark ◽  
Paul N. Bishop ◽  
Anthony J. Day
Keyword(s):  
Macular Degeneration ◽  
Heparan Sulphate ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related ◽  
Zip Code

Essential role of surface-bound complement factor H in controlling immune complex-induced arthritis

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1168
Author(s):  
Nirmal K. Banda ◽  
Gaurav Mehta ◽  
Viviana P. Ferreira ◽  
Claudio Cortes ◽  
Michael K. Pangburn ◽  
...  
Keyword(s):  
Immune Complex ◽  
Essential Role ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor

scholarly journals The role of complement factor H in the pathogenesis of Borrelia infection

2012 ◽  
Vol 66 ◽  
pp. 501-506 ◽  
Author(s):  
Aleksandra Gęca ◽  
Urszula Mazurek ◽  
Małgorzata Muc-Wierzgoń ◽  
Ewa Nowakowska-Zajdel ◽  
Elżbieta Niedworok ◽  
...  
Keyword(s):  
Factor H ◽  
Complement Factor H ◽  
Complement Factor

scholarly journals Two human antibodies to a meningococcal serogroup B vaccine antigen enhance binding of complement Factor H by stabilizing the Factor H binding site

2021 ◽  
Vol 17 (6) ◽  
pp. e1009655
Author(s):  
Nathaniel A. Sands ◽  
Peter T. Beernink
Keyword(s):  
Binding Site ◽  
Human Subjects ◽  
Bacterial Pathogen ◽  
Factor H ◽  
Microbial Pathogens ◽  
Vaccine Antigen ◽  
Complement Factor ◽  
Amino Terminal ◽  
Minimal Contact ◽  
Amino Terminal Domain

Microbial pathogens bind host complement regulatory proteins to evade the immune system. The bacterial pathogen Neisseria meningitidis, or meningococcus, binds several complement regulators, including human Factor H (FH). FH binding protein (FHbp) is a component of two licensed meningococcal vaccines and in mice FHbp elicits antibodies that inhibit binding of FH to FHbp, which defeat the bacterial evasion mechanism. However, humans vaccinated with FHbp develop antibodies that enhance binding of FH to the bacteria, which could limit the effectiveness of the vaccines. In the present study, we show that two vaccine-elicited antibody fragments (Fabs) isolated from different human subjects increase binding of complement FH to meningococcal FHbp by ELISA. The two Fabs have different effects on the kinetics of FH binding to immobilized FHbp as measured by surface plasmon resonance. The 1.7- and 2.0-Å resolution X-ray crystal structures of the Fabs in complexes with FHbp illustrate that the two Fabs bind to similar epitopes on the amino-terminal domain of FHbp, adjacent to the FH binding site. Superposition models of ternary complexes of each Fab with FHbp and FH show that there is likely minimal contact between the Fabs and FH. Collectively, the structures reveal that the Fabs enhance binding of FH to FHbp by altering the conformations and mobilities of two loops adjacent to the FH binding site of FHbp. In addition, the 1.5 Å-resolution structure of one of the isolated Fabs defines the structural rearrangements associated with binding to FHbp. The FH-enhancing human Fabs, which are mirrored in the human polyclonal antibody responses, have important implications for tuning the effectiveness of FHbp-based vaccines.

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