Domain deletions in the human polymeric Ig receptor disclose differences between its dimeric IgA and pentameric IgM interaction

The human polymeric Ig receptor (pIgR), or transmembrane secretory componen t, is basolaterally expressed on secretory epithelial cells; its function i s to transport externally J chain-containing dimeric IgA and pentameric IgM . The ligand-binding extracellular part of this receptor contains five disu lfide-stabilized domains which show considerable homology with the variable domains of Ig chains. The N-terminal domain 1 (D1) mediates the initial no ncovalent ligand interaction. In this study we made deletions of the human pIgR D2 and D3 (pIgR Delta 2,3), or D4 and D5 (pIgR Delta 4,5), to investig ate the influence of these domains in receptor binding and transport of dim eric IgA and pentameric IgM across MDCK cells transfected with the truncate d receptors. Both mutants were found to bind pentameric IgM, but only pIgR Delta 4,5 bound dimeric IgA. These results showed that the two ligands inte ract differently with human pIgR; binding of pentameric IgM apparently depe nds fully on strong interactions with D1, while binding of dimeric IgA in a ddition depends on elements within D2 and/or D3 to support the initial nonc ovalent binding to D1. Moreover, our studies imply that dimeric human IgA b inds differently to pIgR from various species. This observation cautions ag ainst interpretation of functional studies performed with non-homologous re ceptor-ligand pairs.