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

P Crottet, B Corthésy - The Journal of Immunology, 1998 - journals.aai.org
P Crottet, B Corthésy
The Journal of Immunology, 1998journals.aai.org
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 (IgA d) with either recombinant human SC (rSC) or SC
isolated from human colostral milk (SC m). Both complexes exhibited an identical degree of …
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 (IgA d) with either recombinant human SC (rSC) or SC isolated from human colostral milk (SC m). 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 IgA d was achieved at∼ 10 nM SC competitor. Western blot analysis of IgA d digested with intestinal washes indicated that the α-chain in IgA d was primarily split into a 40-kDa species, a phenomenon delayed in rSC-or SC m-IgA d complexes. In the same assay, either of the SCs was resistant to degradation only if complexed with IgA d. In contrast, the κ light chain was not digested at all, suggesting that the F (ab′) 2 region was left intact. Accordingly, IgA d and SC-IgA d digestion products retained functionality as indicated by Ag reactivity in ELISA. Size exclusion chromatography under native conditions of digested IgA d and rSC-IgA d demonstrates that SC exerts its protective role in secretory IgA by delaying cleavage in the hinge/Fc region of the α-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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