STRUCTURAL BASIS FOR THE MULTIPLE FUNCTIONS OF SECRETORY COMPONENT

Abstract

Secretory component (SC) plays a central role in the mucosal immune system. This polypeptide serves as the epithelial cell receptor and transporter for polymeric IgA (pIgA) and protects IgA from proteolysis. To evaluate the structural basis for these functions, we produced a large panel of monoclonal antibodies to human free SC (FSC) and SC bound to secretory IgA (bSC). We examined the reactivity of these antibodies with FSC, bSC and reduced and alkylated sIgA (R-A sIgA) by ELISA, and to membrane SC on a colon carcinoma cell line (HT29) by immunofluorescence.Twenty one of 22 antibodies from fusions in which sIgA was the immunogen bound preferentially to bSC, while 19 of 25 antibodies from FSC fusions were specific to FSC. These specificities were confirmed by reactions with complexes formed in vitro from pIgA and FSC. Few antibodies reacted with both FSC and bSC. Further testing with R-A sIgA allowed definition of at least 5 groups of epitopes on SC. Only a portion of antibodies reactive with one of these epitope groups mediated intense membrane and cytoplasmic immunofluorescent staining of HT29 cells.These results are consistent with the synthesis of SC as an intergal membrane protein. The frequency of unique epitopes on the various physical forms of human SC indicates that this peptide undergos marked changes in tertiary structure or becomes integrated into surrounding structures. These modifications may be related to the various functions of SC.