The J chain is essential for polymeric Ig receptor-mediated epithelial transport of IgA.
نویسندگان
چکیده
Local production of secretory (S)IgA provides adaptive immunologic protection of mucosal surfaces, but SIgA is also protective when administered passively, such as in breast milk. Therefore, SIgA is a potential candidate for therapeutic administration, but its complex structure with four different polypeptide chains produced by two distinct cell types complicates recombinant production. The J chain is critical in the structure of SIgA because it is required for efficient polymerization of IgA and for the affinity of such polymers to the secretory component (SC)/polymeric (p)IgR. To better understand the role of the J chain in SIgA production, we have generated various mutant forms of the human J chain and analyzed the function of these mutants when coexpressed with IgA. We found that the C terminus of the J chain was not required for the formation of IgA polymers, but was essential for the binding of pIgA to SC. Likewise, we found that two of the intrachain disulfide bridges (Cys(13):Cys(101) and Cys(109):Cys(134)) were also required for the binding of pIgA to SC but, interestingly, not for IgA polymerization. Conversely, the last intrachain disulfide bridge (Cys(72):Cys(92)) was not essential for either of these two J chain functions. Finally, we demonstrated that the presence of only Cys(15) or Cys(69) was sufficient to support polymerization of IgA, but that these polymers were mostly noncovalently stabilized. Nevertheless, these polymers bound free SC with nearly the same affinity as pIgA containing wild-type J chain, but were transcytosed by pIgR-expressing polarized epithelial cells at a reduced efficiency.
منابع مشابه
Herve Bazin , and Brian
Polymeric IgA is t ransported from blood to bile by the rat liver (1, 2) in a manner which may be analogous to the transport of polymeric IgA across the mucosal epithelium. Such transport is thought to be mediated by secretory component (SC) 1 an epithelial cell glycoprotein which acts as a receptor for polymeric IgA on these cells (3-8). Fisher et al. (9) recently reported that Ig transport by...
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ورودعنوان ژورنال:
- Journal of immunology
دوره 167 9 شماره
صفحات -
تاریخ انتشار 2001