Nonimmune binding of human immunoglobulin A to type II group B streptococci

Abstract

The binding of 1251-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgAl purified from normal serum. Specific binding was more rapid at 25°C than at 0 or 37°C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90°C for 1 h). Most radioactivity bound to group B streptococci could be displaced (>60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (108 streptococci in 1 ml of buffer) was saturated by approximately 24 ,ug of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgAl, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme-linked immunosorbent-filtration assay showed that both IgAl and IgA2 bound to a type II group B streptococcus bearing the c protein.

Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces

“…Consequently, we have proposed that IgA proteins exhibit protective functions through antibodydependent specific immunity as well as glycan-dependent innate immunity [30]. This concept was confirmed in vitro for other microbial ligand-glycan receptors [1,26,29,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. In addition to E. coli, many other bacteria such as Helicobacter pylori, Streptococcus pneumoniae, Clostridium difficile, Shigella flexneri, Pseudomonas aeruginosa and Neisseria gonorrhoeae, and some viruses (Table 1) interact with epithelial receptors via their glycan moiety.…”

“…Bacteria 0165-2478/$ -see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2009.03.013 Table 1 Examples of glycans as adhesion sites and receptors for selected bacteria and viruses that colonize, or infect, mucosal surfaces (adapted from [1,26,29,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]132] endogenous to the intestinal tract, oral cavity, and probably also the respiratory and genital tracts, are coated in vivo with S-IgA [9,13,17,[31][32][33][34][35][36][37][38][39] that limits their epithelial adherence and penetration, thereby confining them to the mucosal surfaces. Numerous models have demonstrated the role of antibodies, especially S-IgA, in protecting the intestinal and other mucosal tracts.…”

Prevalence of IgA receptors in clinical isolates of Streptococcus pyogenes and Streptococcus agalactiae; Serologic distinction between the receptors by blocking antibodies

“…Theoretically, such antibodies might be required in order for antistreptococcal secretory IgA antibodies to inhibit mucosal adhesion of IgA-binding strains, though the secretory component also appears inhibitory for the streptococcal IgA receptors [25,28]. Whether, at the systemic level, such blocking antibodies might serve as opsonins is unknown but may be suggested by earlier data on antibodies to the c protein of group B streptococci [29,30] and by a recent study with recombinant c protein [31]. An opsonic [32] and protective [33] role of a monoclonal antibody to group A streptococcal IgG Fc-receptor was earlier reported from this laboratory.…”

Fab-Independent Antiadhesion Effects of Secretory Immunoglobulin A on S-FimbriatedEscherichia coliAre Mediated by Sialyloligosaccharides

“…While the IgA1 subtype is exclusively N glycosylated, the protease-resistant IgA2 subtype is additionally characterized by five O-glycosidic chains localized in the hinge region of the molecule (2,3,17). A possible role of these carbohydrates in antiadhesion effects of s-IgA on human pathogens has previously been suggested and supported by experimental evidence (1,18). In this context, mannose residues, which are a regular component of N-linked oligosaccharides on s-IgA, have been reported to be receptors for type 1 fimbriae of Escherichia coli (18).…”