Production and Use of Monoclonal IgA Antibodies Complexed with Recombinant Secretory Component for Passive Mucosal Protection

Abstract

To respond to the constant challenge of their mucosal surfaces by pathogenic organisms, mammals have evolved non-immune protection mechanisms as well as a distinct mucosal immune system, the effector molecule of which is secretory IgA (S-IgA). Mucosal and glandular epithelial cells are able to transcytose dimeric and polymeric IgA by a specific receptor-mediated transepithelial transport mechanism. The polymeric immunoglobulin receptor (poly Ig R) is a member of the immunoglobulin supergene family². The ectodomain of this integral membrane protein is composed of five domains, homologous to variable Ig domains^1,3, the first of which is responsible for binding of the polymeric IgA⁴. Upon binding of IgA at the basolateral surface of epithelial cells, the receptor-IgA complex is endocytosed and during translocation across the cell the interaction of IgA with the receptor is further stabilized by the formation of a disulfide bridge between the poly Ig R fifth domain and one constant domain of the IgA dimer heavy chain⁵. Once at the apical surface of the epithelium, the receptor is cleaved and its entire ectodomain, also called secretory component (SC) remains bound to the IgA⁵. There is some evidence that SC protects IgA dimers against proteolytic degradation⁶. S-IgA antibodies are thus produced locally by a unique collaboration between plasma cells, present in the interstitium of mucosal and glandular tissues, and the overlying epithelial cells.