Characterization of immunoglobulin binding by schistosomes.
Although controversial, schistosomes are believed to cloak themselves in antibody through non-specific interactions with the immunoglobulin (Ig) molecule. The acquisition of host Ig by the schistosome may mask its foreign status and/or interfere with Fc-dependent functions. We report experiments aimed at characterizing the interaction between Ig-Fc and paramyosin, a schistosome Fc-receptor previously reported to bind human IgG. We show that certain Ig classes, in particular murine IgG2b and IgG3, are not only able to bind recombinant paramyosin, but also associate with other parasite proteins. The Fc region of IgG contains four hydrophobic patches, two of which are known to interact with distinct molecules: one in the Cgamma2-Cgamma3 interdomain region bound by protein G, mannose binding lectin (MBL), and the neonatal Fc-receptor (FcRn), and one at the top of the Cgamma2 domain bound by phagocytic FcgammaRs and C1q. We provisionally discounted the involvement of these regions, since IgG binding by paramyosin did not inhibit FcgammaR-mediated NADPH respiratory bursts, and protein G was unable to block IgG binding to paramyosin. Given their apparent low affinity, we postulate hydrogen bonding between reactive residues in a hydrophobic patch at the bottom of the Cgamma3 domain and negatively charged Glu or Asp amino acids in paramyosin.
McIntosh
R S
RS
Institute of Genetics, School of Biology, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2RD, UK.
Jones
F M
FM
Dunne
D W
DW
McKerrow
J H
JH
Pleass
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001666:Binding Sites, Antibody; D006376:Helminths; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D012550:Schistosoma mansoni / Q000276:immunology / Q000378:metabolism*; D014335:Tropomyosin / Q000378:metabolism
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D014335:Tropomyosin; D010447:Peptide Hydrolases