Secretory component delays the conversion of secretory IgA into antigen-binding competent F(ab')2: a possible implication for mucosal defense.

Détails

ID Serval
serval:BIB_89E24BF638F6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Secretory component delays the conversion of secretory IgA into antigen-binding competent F(ab')2: a possible implication for mucosal defense.
Périodique
Journal of Immunology
Auteur(s)
Crottet P., Corthésy B.
ISSN
0022-1767[print], 0022-1767[linking]
Statut éditorial
Publié
Date de publication
1998
Volume
161
Numéro
10
Pages
5445-5453
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Secretory component (SC) represents the soluble ectodomain of the polymeric Ig receptor, a membrane protein that transports mucosal Abs across epithelial cells. In the protease-rich environment of the intestine, SC is thought to stabilize the associated IgA by unestablished molecular mechanisms. To address this question, we reconstituted SC-IgA complexes in vitro by incubating dimeric IgA (IgAd) with either recombinant human SC (rSC) or SC isolated from human colostral milk (SCm). Both complexes exhibited an identical degree of covalency when exposed to redox agents, peptidyl disulfide isomerase, and temperature changes. In cross-competition experiments, 50% inhibition of binding to IgAd was achieved at approximately 10 nM SC competitor. Western blot analysis of IgAd digested with intestinal washes indicated that the alpha-chain in IgAd was primarily split into a 40-kDa species, a phenomenon delayed in rSC- or SCm-IgAd complexes. In the same assay, either of the SCs was resistant to degradation only if complexed with IgAd. In contrast, the kappa light chain was not digested at all, suggesting that the F(ab')2 region was left intact. Accordingly, IgAd and SC-IgAd digestion products retained functionality as indicated by Ag reactivity in ELISA. Size exclusion chromatography under native conditions of digested IgAd and rSC-IgAd demonstrates that SC exerts its protective role in secretory IgA by delaying cleavage in the hinge/Fc region of the alpha-chain, not by holding together degraded fragments. The function of integral secretory IgA and F(ab')2 is discussed in terms of mucosal immune defenses.
Mots-clé
Animals, Antibody Affinity, Antigens, Bacterial/metabolism, Binding Sites, Antibody, Binding, Competitive/immunology, Dimerization, Endopeptidases/metabolism, Hela Cells, Humans, Hydrolysis, Immunity, Mucosal, Immunoglobulin A/metabolism, Immunoglobulin A, Secretory/metabolism, Immunoglobulin Fab Fragments/metabolism, Intestinal Mucosa/enzymology, Intestinal Mucosa/immunology, Kinetics, Lipopolysaccharides/immunology, Lipopolysaccharides/metabolism, Mice, Milk/immunology, Recombinant Proteins/immunology, Recombinant Proteins/metabolism, Secretory Component/genetics, Secretory Component/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 15:53
Dernière modification de la notice
03/03/2018 19:08
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