In collaboration with
University of Oslo, Norway.
Past project's Collaborator
Mélanie DUC (to March 2011)
A striking feature of SIgA is its capacity to adhere selectively to microfold (M) cells in Peyer’s patches; these latter are subsequently able to transport SIgA Ab across the epithelium and to bring them in contact with dendritic cells in the underlying mucosa-associated lymphoid tissue (MALT). In face of the large excess of SIgA in the intestinal lumen, intrinsic passage of the antibody (Ab) or immune complexes (IC) remains limited. In this context, we previously postulated that upon binding of the antigen (Ag), SIgA experiences conformational changes that result in increased binding to the so far unidentified IgA receptor on the apical surface of M cells, Conformational differences in pIgA- or SIgA-based IC as compared with the corresponding free Ab may also explain differential mucus binding properties and immune exclusion. To address the question of Ag-mediated structural changes in pIgA and SIgA, we combined pIgA and SIgA with three antigenic structures of increased complexity, namely a protein (Clostridium difficile toxin A), a virus (rotavirus), and a bacterium (Shigella flexneri), and examined their sensitivity and receptor binding capacity in comparison with free Ab.
We found modified sensitivity of the three Ags assayed after exposure to proteases from intestinal washes. Ag binding further impacted on the immunoreactivity toward polyclonal antisera specific for the heavy and light chains of the Ab, as a function of the Ag size. These conformational changes promoted binding of the SIgA-based immune complex as compared to the free Ab to cellular receptors (FcaRI and polymeric immunoglobulin receptor) expressed on the surface of premyelocytic and epithelial cell lines. Results obtained with pIgA/SIgA and C. difficile toxin A are presented in Table 1. These data reveal that Ag recognition by SIgA triggers structural changes that confer to the Ab enhanced capacity to bind specific receptors. This identifies immune complexes as particular structural entities integrating the presence of bound Ags, and adds to the known function of immune exclusion and mucus anchoring by SIgA.