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

Details

Serval ID
serval:BIB_89E24BF638F6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Secretory component delays the conversion of secretory IgA into antigen-binding competent F(ab')2: a possible implication for mucosal defense.
Journal
Journal of Immunology
Author(s)
Crottet P., Corthésy B.
ISSN
0022-1767[print], 0022-1767[linking]
Publication state
Published
Issued date
1998
Volume
161
Number
10
Pages
5445-5453
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Create date
25/01/2008 14:53
Last modification date
20/08/2019 14:48
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