Oligosaccharide side chains on human secretory IgA serve as receptors for ricin.
Secretory IgA (sIgA) Abs are polymeric Igs comprised of two or more IgA monomers joined together at their C termini and covalently associated with a 70-kDa glycoprotein called secretory component. As the predominant Ig type in gastrointestinal sections, sIgA Abs are centrally important in adaptive immunity to enteropathogenic bacteria, viruses, and toxins. In this study, we demonstrate that sIgA Abs may also function in innate defense against ricin, a naturally occurring, galactose-specific plant lectin with extremely potent shiga toxin-like enzymatic activity. In lectin blot overlay assays, we found that ricin bound to secretory component and the H chain of human IgA, and this binding was inhibited by the addition of excess galactose. The toxin also recognized IgM (albeit with less affinity than to IgA), but not IgG. Ricin bound to both human IgA1 and IgA2, primarily via N-linked oligosaccharide side chains. At 100-fold molar excess concentration, sIgA (but not IgG) Abs inhibited ricin attachment to the apical surfaces of polarized intestinal epithelial cells grown in culture. sIgA Abs also visibly reduced toxin binding to the luminal surfaces of human duodenum in tissue section overlay assays. We conclude that sIgA Abs in mucosal secretions may serve as receptor analogues for ricin, thereby reducing the effective dose of toxin capable of gaining access to glycolipid and glycoprotein receptors on epithelial cell surfaces.
Mantis
Nicholas J
NJ
Gastrointestinal Cell Biology Laboratory, Children's Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. nmantis@wadsworth.org
Farrant
Stephanie A
SA
Mehta
Simren
S
D016764:Cell Polarity; D004386:Duodenum / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000737:chemistry* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D012276:Ricin / Q000378:metabolism* / Q000633:toxicity; D012635:Secretory Component / Q000378:metabolism
D007071:Immunoglobulin A, Secretory; D007143:Immunoglobulin Heavy Chains; D009844:Oligosaccharides; D012635:Secretory Component; D012276:Ricin