Secretory component as the mucosal transport receptor: separation of physicochemically analogous human IgA fractions with different receptor-binding capacities.
This paper describes the separation and characterization of several IgA fractions from the same human monoclonal source, based on their ability to bind secretory component (SC). The study was undertaken to elucidate features of the immunoglobulin-binding site for SC, and to examine the dependence of mucosal transport on IgA-SC interaction. Enrichment or depletion of SC-binding activity was accomplished on an affinity adsorbant made with SC from human colostral whey. The affinity-purified human IgA fractions contained IgA polymers and were 77% active in rebinding to the adsorbant; this activity was diminished significantly by direct radioiodination. The non-adherent IgA fractions contained both polymer and monomer, and were only 8% active in rebinding to the adsorbant. When the polymer and monomer components were separated from each other, the non-adherent polymer was found to resemble the affinity-purified fraction by all criteria examined including J-chain content, except that the SC-binding capacity was greater than five-fold lower. These findings have two implications for the SC-binding site on human IgA: first, the presence of J-chain is insufficient to bestow IgA with SC-binding activity; second, a critical tyrosine participates in maintaining the SC-binding region, possibly on the IgA heavy chain. The relationship between SC binding and mucosal transport was tested in the rat hepatobiliary model. All radiolabeled human IgA fractions were captured rapidly from blood by the rat liver, but only the SC-binding fractions underwent substantial intact transport to bile (greater than 70% of the injected dose). Even though a nominal proportion of the SC-non-adherent IgA appeared in bile (4-15% of the dose), most IgA in these fractions was rapidly degraded within the liver. Thus, only a small amount of monomeric and polymeric IgA can use alternative receptors to get to bile by diversion from the degradative pathway. Polymeric IgA can undergo efficient transport across the cell, strictly conditional on a high binding capacity for SC. This demonstrates that membrane SC is the receptor conferring specificity on the mucosal-transport pathway.
D000818:Animals; D015703:Antigens, CD; D001646:Bile / Q000276:immunology; D001665:Binding Sites; D001693:Biological Transport, Active; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007128:Immunoglobulin Fragments; D008099:Liver / Q000276:immunology; D008297:Male; D009092:Mucous Membrane / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000378:metabolism*; D012635:Secretory Component; D013045:Species Specificity
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007128:Immunoglobulin Fragments; D011961:Receptors, Fc; D012635:Secretory Component