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*Substance via MeSH
The Journal of Immunology, 1998, 161: 5445-5453.
Copyright © 1998 by The American Association of Immunologists

Secretory Component Delays the Conversion of Secretory IgA into Antigen-Binding Competent F(ab')2: A Possible Implication for Mucosal Defense1

Pascal Crottet2,* and Blaise Corthésy3,*,{dagger}

* Institut Suisse de Recherches Expérimentales sur le Cancer, Epalinges, Switzerland; and {dagger} Division d’Immunologie et d’Allergie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

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 ~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.




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