Anti-Gal binds to pili of Neisseria meningitidis: the immunoglobulin A isotype blocks complement-mediated killing.
alpha 1,3-Galactosyl antibodies (anti-Gal) are ubiquitous natural human serum and secretory polyclonal antibodies that bind to terminal galactose-alpha 1,3-galactose (alpha-galactosyl) residues. Serum immunoglobulin G (IgG) anti-Gal can block alternative complement pathway-mediated lysis of representative gram-negative enteric bacteria that bind it to lipopolysaccharide alpha-galactosyl structures, thereby promoting survival of such bacteria in the nonimmune host. We wanted to know whether anti-Gal also could bind to the lipooligosaccharides (LOS) of Neisseria meningitidis. To our surprise, we found that serum and secretory anti-Gal bound to pili but not to LOS of certain strains. This suggested the presence of an immunogenic pilus carbohydrate epitope. Mild periodate oxidation of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated outer membrane preparations from strains that bound anti-Gal followed by labeling of the neoaldehyde groups resulted in the labeling of bands that corresponded to pilin and LOS, confirming that pilin contains carbohydrate structures. A Bandeiraea simplicifolia lectin that also binds terminal alpha 1,3-galactosyl residues also bound to pilin. Serum IgG, IgA, and IgM anti-Gal as well as colostral secretory IgA anti-Gal bound to pilin, as judged by immunoblotting, and to the pili of intact piliated organisms, as judged by immunoelectron microscopy. Total serum anti-Gal (IgG, IgA, and IgM) and purified serum IgA1 anti-Gal, but not its purified IgG isotype, blocked complement-mediated lysis of a piliated meningococcal strain that bound anti-Gal to its pili. Colostral anti-Gal secretory IgA blocked killing of the same strain. Thus, anti-Gal IgA may promote disease when it binds to the pili of N. meningitidis strains.
Hamadeh
R M
RM
Centre for Immunochemistry, University of California, San Francisco, USA.
Estabrook
M M
MM
Zhou
P
P
Jarvis
G A
GA
Griffiss
J M
JM
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology*; D004187:Disaccharides / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology*; D006384:Hemagglutination; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D011817:Rabbits
D004187:Disaccharides; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; C055075:galactosyl-(1-3)galactose; D003165:Complement System Proteins